Scholarly article on topic 'Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapies on people living with HIV: A systematic review and meta-analysis'

Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapies on people living with HIV: A systematic review and meta-analysis Academic research paper on "Psychology"

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Abstract of research paper on Psychology, author of scientific article — Yang Yang, Yan-Hui Liu, Hong-Fu Zhang, Jing-Ying Liu

Abstract Objective To assess the effects of mindfulness-based therapies (MBTs) on the outcomes of people living with HIV. Methods During 2014, we searched the PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and CBM databases to identify randomized and non-randomized controlled studies which compared participants receiving mindfulness-based therapies (MBTs), including mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), with participants in control groups. The psychological, biochemical, clinical, and behavioral outcomes of the study participants were analyzed. Two separate reviewers independently performed the study selection, data extraction, and quality assessment tasks, and a meta-analysis of selected studies was performed using RevMan software. Results Seven articles describing results obtained with a total of 620 HIV-infected individuals enrolled in six randomized trials and one quasi-experimental trial were included in the final meta-analysis. The overall methodological quality of the studies was moderate, as most study criteria were unclear and subject to a high risk of bias. Patients receiving MBT experienced significantly decreased feelings of stress after 8 weeks (p = 0.03) of MBT, and decreased feelings of depression after both 8 weeks (p = 0.04) and 6 months (p = 0.02). Additionally, some patients receiving MBSR training or MBCT showed improved CD4+ counts at 8 weeks and 6 months, respectively. Conclusion While MBT produced psychological benefits in HIV infected patients, any improvements in CD4+ counts were not robust. Additional studies with longer term follow-up periods and larger sample sizes are required to ascertain the effectiveness of such interventions.

Academic research paper on topic "Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapies on people living with HIV: A systematic review and meta-analysis"

Accepted Manuscript

Effectiveness of mindfulness-based stress reduction and mindfulness based cognitive therapies on people living with HIV: A systematic review and meta-analysis

Yang Yang, Yan-Hui Liu, Hong-Fu Zhang, Jing-Ying Liu

PII: S2352-0132(15)00065-4

DOI: 10.1016/j.ijnss.2015.07.003

Reference: IJNSS 127

To appear in: International Journal of Nursing Sciences

Received Date: 17 March 2015

Revised Date: 10 July 2015

Accepted Date: 29 July 2015

Please cite this article as: Y. Yang, Y.-H. Liu, H.-F. Zhang, J.-Y. Liu, Effectiveness of mindfulness-based stress reduction and mindfulness based cognitive therapies on people living with HIV: A systematic review and meta-analysis, International Journal of Nursing Sciences (2015), doi: 10.1016/ j.ijnss.2015.07.003.

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Effectiveness of mindfulness-based stress reduction and mindfulness based cognitive therapies on people living with HIV: A systematic review and meta-analysis

Yang Yang, Yan-Hui Liu*, Hong-Fu Zhang, Jing-Ying Liu

School of Nursing, Tianjin University of Traditional Chinese Medicine, E-mail:

* Corresponding author. E-mail: yh_liu888@163.com(Y-H. Liu)

Author contributions

All authors have agreed on the final version and meet at least one of the following criteria [recommended by the ICMJE (http://www.icmje.org/ethical_1author.html)]: •substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data;

• drafting the article or revising it critically for important intellectual content.

Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapies on people living with HIV: A systematic review and meta-analysis Abstract

Objective: To assess the effects of mindfulness-based therapies (MBTs) on the outcomes of people living with HIV.

Methods: During 2014, we searched the PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and CBM databases to identify randomized and non-randomized controlled studies which compared participants receiving mindfulness-based therapies (MBTs), including mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), with participants in control groups. The psychological, biochemical, clinical, and behavioral outcomes of the study participants were analyzed. Two separate reviewers independently performed the study selection, data extraction, and quality assessment tasks, and a meta-analysis of selected studies was performed using RevMan software.

Results: Seven articles describing results obtained with a total of 620 HIV-infected individuals enrolled in six randomized trials and one quasi-experimental trial were included in the final meta-analysis. The overall methodological quality of the studies was moderate, as most study criteria were unclear and subject to a high risk of bias. Patients receiving MBT experienced significantly decreased feelings of stress after 8 weeks (p = 0.03) of MBT, and decreased feelings of depression after both 8 weeks (p = 0.04) and 6 months (p = 0.02). Additionally, some patients receiving MBSR training or MBCT showed improved CD4+ counts at 8 weeks and 6 months, respectively.

Conclusion: While MBT produced psychological benefits in HIV infected patients, any improvements in CD4+ counts were not robust. Additional studies with longer term follow-up periods and larger sample sizes are required to ascertain the effectiveness of such interventions.

Keywords

HIV, MBCT, MBSR, Meta-analysis, Mindfulness, Systematic review

1. Introduction

The development of combined antiretroviral therapy has enabled HIV-infected individuals to live for longer periods of time [1]. The WHO and UNAIDS estimated that 35 million people world-wide were living with HIV at the end of 2013 [2]. The HIV virus infects activated CD4+ T lymphocytes, causing their progressive depletion and subsequent defects in the immune system that lead to various diseases and cancers [3]. In addition to producing physiological effects, the psychological impact of having HIV/AIDS can affect disease progression as well as a patient's clinical outcome[4]. A recent study [5] reported a higher prevalence of psychological problems, such as feelings of stress, depression, and anxiety, among people living with HIV when compared to people in the general population. This may be due not only to the illness, but also to various social factors. The various mental disorders (stress, anxiety, and depression) found among people living with HIV have recently received greater attention by researchers. These psychological problems might further suppress the immune system and accelerate disease progression, causing an HIV-infected individual to develop AIDs more quickly [6]. Furthermore, such psychological problems can impair a patient's ability to understand and follow prescribed treatment regimens, leading to poor cART adherence and treatment results [7]. The WHO has stated that enhancing and preserving patient quality of life should be a primary outcome goal of contemporary HIV therapy, and that new treatment strategies should produce marked improvements in patient health [8]. Therefore, equipping HIV infected patients with the skills and coping strategies needed manage their physiological and psychological problems has become an integral part of providing comprehensive care to HIV/AIDS patients.

Mindfulness-based therapies (MBTs) evolved from Western psychology as practiced in the late 1970s. This type of therapy seeks to have people live in the present moment, and be non-judgemental, accepting, patient, open, curious, kind, and "non-doing" [9]. It is hoped that through practicing mindfulness, patients will build the skills needed to pay total attention to the present moment, and accept their physical pain or psychological distress with a non-judgmental awareness [10]. It has been suggested that mindfulness exerts its effects via four mechanisms: attention regulation, body awareness, emotion regulation, and changes in perspective regarding one's self [11]. Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT) are two of the most widely used mindfulness-based therapies, and are designed

to provide therapeutic benefits to people who practice them [12]. MBSR therapy is a structured treatment program originally developed to manage chronic pain, and is now widely used to reduce the incidence and severity of psychological morbidities associated with chronic illnesses [9]. MBCT, combines elements of MBSR therapy, cognitive psychology, and cognitive-behavioral therapy, and was initially designed to treat people with a history of recurrent depression. It is currently used to treat emotional and behavioral disorders [13].

The results of previous systematic reviews and meta-analyses have suggested that MBSR training and MBCT might be effective interventions for use in relieving chronic pain [14-15], lowering blood pressure [16]), as well as improving psychological health (depression, stress, anxiety), and quality of life [17-19]. The current systematic reviews concerning the uses of MBSR training and MBCT have mainly focused on studies involving patients with chronic diseases such as cancer [19-24], chronic pain [14, 25], psychiatric disorders [17, 18, 26], cardiovascular diseases [16], and crowd diseases [26-28]. Although the results of some clinical studies investigating the effects of MBSR training and MBCT on people living with HIV have been reported, their findings have not been widely publicized or acknowledged. Our current meta-analysis was performed to assess the short- and long-term effects of MBSR training and MBCT on people living with AIDS, and compare those effects with those provided by control interventions. Such information might provide evidence regarding the usefulness of MBSR training and MBCT in promoting the physical and mental health of people living with HIV/AIDS. 2. Methods

2.1 Eligibility criteria:

Trials with the following characteristics were included in the meta-analysis.

2.1.1 Types of study designs:

Randomized controlled trials (RCTs) and quasi-experimental trials.

2.1.2 Types of participants:

Patients diagnosed as HIV-infected, regardless of age, infection duration or severity.

2.1.3 Types of interventions:

Eligible trials included those that compared patients receiving MBSR training or MBCT with patients in either an inactive control group (no treatment or standard care treatment) or who were receiving some any other type of active treatment. Studies describing interventions that were

based on mindfulness, but were not specifically designated as an MBSR or MBCT program, were excluded.

2.1.4 Types of outcomes:

Primary outcomes: CD4+ cell counts, feelings of stress, distress or depression in the physical and psychological aspects of life, respectively. Secondary outcomes: HIV-RNA load, positive and negative effects of MBT on anxiety, mindfulness, physical symptomatology, mental health, results shown on a checklist of side effects of HIV infection, and the impact of those side effects on the patient's physical, psychological, and clinical health. Patient behavioral outcomes and the safety MBT were also assessed.

2.1.5 Length of follow-up:

Both the short-term effects (determinations made ~ 8 weeks after intervention) and long-term effects (determinations made ~ 6 months after intervention) of MBT were analyzed.

2.2 Search strategy

We used both MeSH terms and free text terms to search the following electronic databases without date restrictions: PubMed/MEDLINE, Embase, Web of Science, the Cochrane Library, and CBM. We also retrieved references cited in the included studies. Studies published in either Chinese or English were considered, and web sites such as http://mindfulness teachers uk.org.uk and http://www.mindful experience.org/ were searched to find grey literature. The following strategy is an example of one used to electronically search the PubMed database: (HIV [MeSH Terms] OR Human Immunodeficiency Virus [Title/Abstract] OR AIDS Virus [Title/Abstract] OR Acquired Immunodeficiency Syndrome Virus [Title/Abstract]) AND (mind body therapies [MeSH Terms] OR mindfulness [Title/Abstract] OR Mindfulness-Based Stress Reduction [Title/Abstract] OR MBSR [Title/Abstract] OR mindfulness based cognitive therapy [Title/Abstract] OR MBCT [Title/Abstract]).

2.3 Study selection

After removing duplicated material, two authors independently screened for titles of articles and abstracts of manuscripts which satisfied our eligibility criteria. Next, the full-texts of manuscripts were checked to determine if they described trials that should be included in this systematic review. Disagreements between the two reviewers were resolved by a third reviewer.

2.4 Data Extraction

Each study's characteristics (participants, interventions, control conditions, outcome measures and findings) were extracted independently by two different reviewers. The study investigator(s) was contacted if the required data were not available in their published manuscripts. A third independent reviewer helped to resolve any disagreements.

2.5 Risk of bias

The Cochrane 'risk of bias' tool [29] was used to test for bias and assess the methodological quality of each paper based on six criteria: sequence generation, allocation concealment, blinding of participants, personnel or outcome assessors, completeness of outcome data, and selectivity of outcome reporting. The degree to which a paper satisfied these criteria was assessed by one reviewer, and checked by a second reviewer. A third reviewer was invited to resolve any differences of opinion.

2.6 Data analysis and synthesis

The outcomes of studies were assessed using Review Manager software (Version 5.2, The Nordic Cochrane Centre, Copenhagen). For continuous outcomes, pooled effects were assessed by calculating their standardized mean differences (SMDs) with 95% confidence intervals (CIs). When two or more groups showed no statistically significant differences at baseline, mean differences (SMDs) were calculated using the final values for the particular outcomes (post-intervention outcomes). When a significant difference existed between an intervention and control group, the standardized mean difference (SMD) was calculated using the difference in the changes in values from baseline values. The mean change was obtained by subtracting the final mean value from the mean value at baseline. Standard deviations (SDs) for statistical results were calculated using a formula in the Cochrane Handbook 30. Correlations between baseline and follow-up values were obtained from a comparable study or by using the correlation coefficient (r = 0.5) suggested in the Cochrane Handbook [29].

Statistical heterogeneity among the reviewed studies was quantified by determining values for I2; where I2 < 30%, I2 > 50%, and I2 > 75% were defined as moderate, substantial, and considerable heterogeneity, respectively. To eliminate clinical heterogeneity, we conducted subgroup analyses based on the type of intervention (MBSR therapy or MBCT) and control group used in various studies (active control group or inactive group). Additionally, sensitivity analyses were performed by excluding a single study and then comparing the results of studies with a high risk for domain

selection bias, detection bias or attrition bias, with the results of studies having a low risk for the selected particular bias. This type of analysis allowed us to obtain more stable results. 3. Results

3.1 Study selection

Our electronic search identified a total of 230 citations for reports concerning either MBSR therapy or MBCT. After excluding duplicates, 171 studies satisfied our eligibility requirements, and full-text reports were obtained for 31 studies. Among those 31 studies, 24 did not fulfill our inclusion criteria for one of the following reasons: they did not investigate MBSR therapy or MBCT (n = 14), or HIV- infected patients (n = 6), or did not include a control group (n = 4). Finally, six randomized controlled trials and one quasi-experimental study were included in our meta-analysis [31-37]. No additional trial was later included after retrieving references cited in the original seven included studies. A flow chart describing our search strategy and article retrieval results is shown in Fig. 1.

3.2 Study characteristics

The seven included studies (six randomized controlled trials [31-36] and one quasi-experimental study [37]) were published from 2003 to 2014 (Table), and were conducted in Canada [33], Spain [37], Iran [35], and the USA [31, 32, 34, 36], respectively. The number of participants in the individual studies ranged from 34 to 173, and a total 620 participants were enrolled in all seven studies. All study participants had been diagnosed as HIV/AIDS, and the experimental group in each study received intervention with MBCT or MBSR training. Regarding control groups, three trials [32, 35, 36] incorporated an active control treatment which was either a 1-day seminar or Education and Support (ESC) meeting. The remaining four studies [31, 33, 34, 37] incorporated either a placebo group or standard control group (TAU, routine follow-up, wait-list control or comparison group). All study participants were 25 to 64 years old.

3.3 Intervention characteristics

MBSR training was used in six studies [31-36] and MBCT in one study [37]. Both types of therapy were administered for 1.5-2.5 h/week during a program that lasted 8 or 10 weeks. Additionally, the participants performed a daily homework assignment which required 30-43 minutes of time each day, six days per week. There was little variation among the interventions used in the seven included studies.

3.4 Study quality (risk of bias)

We used the Cochrane risk of bias tool to assess the methodological quality of five randomized controlled trials, and the results are presented in Fig. 2. We found that two studies did not report details of their randomization methods [32, 35]. In another study, a blinded design could not be used due to the nature of MBT, and only one study reported that participants were blinded to outcome assessments [32]. Five studies reported unbalanced or unreasonable participant withdrawals, and only two studies included an intention-to-treat analysis [33, 34]. Based on criteria in the Cochrane Handbook, we were unable to assess our meta-analysis for publication bias because there were < 10 included studies.

3.5 Outcomes

The seven studies in our meta-analysis reported five types of outcomes, which included psychological symptoms (perceived stress [31, 33, 34 ], anxiety [33, 37], depression [33, 34, 37], mindfulness [34], positive-negative affect [34]), biochemical indicators (i.e. CD4+ count [32, 35, 37]), quality of life [37], clinical outcomes [35], and behavioral outcomes [37]. Additionally, the safety of MBT intervention was also assessed. 3.5.1 Psychological outcomes

Four trials (with 216 participants receiving MBSR training in three trials [31, 33, 34] and 39 participants receiving MBCT in one trial [37]) used the perceived stress scale (PSS-10) to examine the effects of MBT on psychological stress ( Figs 3 and 4). Our meta-analysis analysis revealed a significant difference between an MBT group and a control group concerning their levels of stress starting at 6 months (SMD = -0.85, 95% CI: -1.61 to -0.08, p = 0.03). Moreover, a subgroup analysis across different types of intervention also indicated that MBSR training could reduce patient stress after 6 months of practice (SMD = -0.41, 95% CI: -0.71 to -0.11, p = 0.007). Additionally, MBCT produced significant effects on stress in both the short- (SMD = -1.18, 95% CI: -1.86 to -0.49, p = 0.0008) and long-term (SMD = -2.00, 95% CI: -2.84 to -1.17, p = 0.000) time frames.

Our meta-analysis of three RCTs (two using MBSR training [33-34] and one using MBCT [37]) showed that MBT significantly improved symptoms of depression in both the short-term and long-term (SMD = -0.35, 95% CI: -0.68 to -0.01, p = 0.04; SMD = -0.47, 95% CI: -0.86 to -0.08, =

0.02, respectively). Furthermore, a subgroup analysis across interventions showed that MBSR training produced a statistically significant long-term effect (SMD = -0.31, 95% CI: -0.61 to -0.01, p = 0.04). The study conducted by Gonzalez-Garcia showed that MBCT had a positive effect on depression in both the short-term and long-term (SMD = -0.83, 95% CI: -1.49 to -0.17, p = 0.01; SMD = -1.02, 95% CI: -1.74 to -0.30, p = 0.005, respectively; Figs 5 and 6). Two trials measured the effects of MBT on patient anxiety using the Hospital Anxiety and Depression Scale (HADS) [33] and the Beck Anxiety Inventory (BAI) [37], respectively. The results showed that MBCT may have had a slight long-term (6 months) effect on anxiety (SMD = -0.74, 95% CI: -1.43 to -0.04). Previously, both Duncan LG et al. [34] and Gayner B et al. [33] used the Positive and Negative Affect Schedule (PANAS) to analyze the positive and negative effects of MBSR training. Our meta-analysis revealed that MBSR had positive effects on people living with HIV after 6 months of training (SMD = 0.42, 95% CI: 0.08 to 0.76, p = 0.01). Additionally, Duncan LG et al. [34] and Gayner B et al.[33] used the Five Factor Mindfulness Questionnaire (FFMQ) and The Mindfulness Measure (TMS), respectively, to measure changes in mindfulness. Duncan LG, et al. [34] reported on four factors examined by the FFMQ, and Gayner B et al. reported that participants in a MBSR group experienced significantly increased levels of mindfulness after 8-weeks of training (SMD = 1.16, 95% CI: 0.75 to 1.57,p = 0.00) and also during a 6-month follow-up period (SMD = 0.75, 95% CI: 0.35 to 1.15, p = 0.00). 3.5.2 Biochemical outcomes

Three trials reported CD4+ cell counts for their participants. Two of the trials used an active control design [32, 35] and one used an inactive control design [37]. The pooled results of these two trials can be seen in the Figs 7 and 8. There was no significant difference between the CD4+ counts of patients who received MBT and control subjects at either an 8-week or 6-month time period. A subgroup analysis revealed an increase in CD4+ cell counts only in the study conducted by Gonzalez Garcia et al. [37], and that increase occurred at 6 months (SMD = 0.76, 95% CI: 0.07 to 1.46, p = 0.03).

Two trials reported the effect of MBT on HIV RNA levels, and neither study found any difference between experimental and control groups after 8 weeks of MBSR training. Additionally, Weston E, et al. 2012 [36] showed that MBSR training did not affect the levels of high sensitivity C-reactive protein (hsCRP) and D-dimer in participants at 3 and 12 months (p > 0.10 compared

with the control group)..

3.5.3 Quality of live, clinical outcomes, and behavioral outcomes

A study by Gonzalez-Garcia M, et al [37] revealed a significant improvement in patient quality of life at both 8 weeks (SMD = -23.30, 95% CI: -37.67 to -8.93, p = 0.001) and 20 weeks (SMD = -32.7.30, 95% CI: -46.52 to -18.88, p= 0.000). Furthermore, SeyedAlinaghi S, et al. [35] reported significantly enhanced physical and mental outcomes in a group of patients receiving MBSR training when compared with a group receiving Education and Support (ESC); additionally, the favorable effects were sustained for up to 12 months. However, that study found no significant difference between the two groups regarding their behavioral outcomes as demonstrated by cART adherence, eating a healthy diet, and smoking after the intervention [37].

3.5.4 Safety

While no trial in our meta-analysis reported adverse events, a total of 42 participants dropped out of studies due to dissatisfaction with the program, health issues, emotional issues, or the amount of time required and intensive nature of the program. 4. Discussion

4.1 Summary of main results

This is the first systematic review and meta-analysis to examine the effects of MBSR training and MBCT on psychological outcomes, biochemical parameters, quality of life, clinical outcomes, and behavioral outcomes, in HIV infected patients. Our results indicate that MBT decreased the levels of stress in patients at 8 weeks, and decreased symptoms of depression at 8 weeks and 6 months.

4.2 Applicability of evidence

HIV infection is characterized by huge variability in the onset age, a variety of clinical symptoms, and a long period of illness. Additionally, HIV/AIDs patients often suffer from serious physical and psychological conditions. The trials included in our meta-analyses were conducted in both developed and developing countries. Furthermore, they enrolled both young and adult patients with a confirmed HIV infection, as well as patients with different levels of disease severity. Some of the patients were receiving antiretroviral therapy, while others were not. Because our analysis included a wide range of populations, it could be argued that our results apply to the majority of people living with HIV/AIDs.

4.3 Quality of evidence

This analysis included a small number of trials, and only one trial reported the effect of MBCT on people infected with HIV. This indicates that the use of mindfulness therapy in treating HIV remains in an exploratory phase. Additionally, the overall quality of evidence provided in the included studies was low, and our results may have been affected by bias.

4.4 Agreement and disagreement with other systematic reviews Our findings regarding the ability of MBT to decrease stress in HIV-infected patients on a long-term basis were in agreement with findings in Chiesa's study [26], which found no significant difference in long-term stress reduction in healthy individuals assigned to a MBT intervention group or control group. However, another study [38] reported that MBT had a small effect size (0.32) on reducing stress in adults with chronic conditions. Reviews of studies conducted with cancer patients suggested an even more significant effect of MBT on patient stress (overall effect sizes of 0.58 to 0.71 [20-21].

Our results showed that MBT was marginally beneficial for relieving symptoms of depression (SMDs = 0.35 for 8 weeks and 0.47 for 6 months), and this result was similar to previously reported findings [15, 17]. Additionally, Clara Strauss et al. [17] reported findings that were consistent with ours from a subgroup analysis conducted across MBCT and MBSR training. In that subgroup analysis MBCT, but not MBST, was shown to be significantly effective for treating depression. Originally, MBCT was found to be effective for reducing the incidence of relapse among people who had experienced > 3 episodes of depression [39]. Our review provides additional evidence that MBCT might also be effective in people with a current diagnosis of a depressive disorder.

Our meta-analysis included only a small number of studies concerning the effect of MBT in treating anxiety, which makes the findings less than robust. Our negative results regarding the effects of MBT on anxiety were consistent with those reported by both Strauss et al. [17] and Lakhan et al. [15]. However, another previous meta-analysis found a moderate to high effect size of anxiety among people with chronic diseases, and also breast cancer patients (SMDs = 0.47 and 0.51~0.73, respectively) [20, 25, 38].

Regarding biomedical outcomes, some previous studies reported that MBSR training could increase plasma cortisol levels, extend cell longevity [40-41], promote the recovery of functional T cells [42], and improve plasma levels of IGF-1 and antigen-specific IgM and IgG 3 [43]. These

results compliment our finding regarding the effect of MBT on CD4+ counts. Additionally, two pilot trials [45-46] reported that MBSR therapy significantly improved both the CD4+ counts and psychological status of people living with HIV. MBSR training not only improved the attitudes (less negativity) of the patients, but also decreased their degrees of reactivity and impulsivity, improved their levels of self-care, and increased their perceived value of socializing with other people. Finally, Gallegos et al. [44] recently reported that MBSR training might benefit the hypothalamic-pituitary-adrenal (HPA) axis and improve the emotional outcomes of older adults.

5. Limitations

Our meta-analysis has some limitations that should be mentioned. The first limitation concerns the experiment design; as only three studies [32, 35, 36] included an active control group and the other four studies had an inactive control group [31, 33, 34, 37]. Future studies should include an active control therapy to better demonstrate the benefits of MBT. Second, the studies in our meta-analysis were of only of moderate methodological quality, because their criteria were unclear, and their design permitted a high risk of bias, which inevitably affected the results of our analysis. Third, four studies only used only six months as a cut-off time for judging the long-term effects of therapy, while one trial used a 12 month time period for this purpose. For people living with HIV and experiencing a current episode of physical or mental disorders, a considerably longer followup period would allow for a more precise evaluation of the long- term effects of a therapy. Fourth, although we used a comprehensive search strategy to retrieve existing trials, due to language and other limitations, only seven studies were included in our analysis, and this might have influenced the robustness of our evidence. Lastly, due to geographical and cultural differences, the results of the included studies might not be directly applicable to Chinese HIV/AIDS patients; therefore, clinical practitioners should consider racial and cultural differences when attempting to apply our results.

6. Implications for further research

Reich et al. [47] reported that the baseline biomarkers of study participants can influence the benefits they receive from MBSR training, and that adherence to an intervention protocol is also a key factor for ensuring that patients benefit from MBSR therapy [36, 48].Although our meta-analysis contained no information regarding protocol adherence, our findings clearly showed that MBT was more effective for treating stress and depression than for treating anxiety. Therefore,

we caution against offering MBT as a first line intervention to people experiencing a primary anxiety disorder. Additionally, MBCT was better than MBSR therapy for improving symptoms of depression among people living with HIV, indicating that intervention methods should be carefully selected and based on specific symptoms exhibited by a patient. 7. Conclusions

This systematic review showed that MBT had a long-term effect on stress and both a short- and long-term effect on depression in people living with an HIV infection. Our results concerning the effects of MBT on anxiety and CD4+ counts in intervention and control groups were ambiguous. More robust studies with longer follow-up times are required to establish the actual efficacy of MBT intervention in HIV/AIDS patients.

Acknowledgments

There was no Financial support for this research. Conflict of interest

No conflict of interest has been declared by the authors. References

1.Mrus JM, Leonard AC, Yi MS, Sherman SN, Fultz SL, Justice AC, et al. Health-related quality of life in veterans and non-veterans with HIV/AIDS. J Gen Intern Med 2006; 21(Suppl 5): S39-47.

2.WHO. Date and statistics. Global summary of the HIV/AIDS epidemic. Available at http://www.who.int/hiv/data/epi core dec2014.png?ua=1 Access in December 2013

3.Cooper A, Garcia M, Petrovas C, Yamamoto T, Koup RA, Nabel GJ, et al.. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature 2013; 498: 376-9.

4.Evans DL, Leserman J, Pedersen CA, Golden RN, Lewis MH, Folds JA, et al. Immune correlates of stress and depression. Psychopharmacology Bulletin. 1989; 25(3): 319-24.

5.Lowther K, Selman L, Harding R, Higginson J. Experience of persistent psychological symptoms and perceived stigma among people with HIV on antiretroviral therapy (ART): a

systematic review. Int J Nurs Stud 2014; 51(8): 1171-89.

6.Lu SH, Tang XP, Deng XL, Chen WL, Hu RX. Relationship between psychological distress and T lymphocyte in HIV/AIDS patients. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za

Zhi. 2009; 23(1): 23-5. [Article in Chinese]

7.Yunusa MA, Njoku CH, Obembe A. Self-reported adherence to treatment: a study of socioeconomic factors and psychiatric morbidity among male and female patients with HIV infection in Sokoto, Nigeria. Niger J Med 2014; 23(1): 33-9.

8.WHO. Global health sector strategy on hiv/aids 2011-2015 2011. strategic direction 1: Optimize hiv prevention, diagnosis, treatment and care outcomes. Available at

http://whqlibdoc.who.int/publications/2011/9789241501651 eng.pdf?ua=1Access in November 21, 2014.

9.Kabat-Zinn. Full Catastrophe living: using the wisdom of your body and mind to face stress, pain and illness. Delacourt. New York, NY, USA, 1990.

10.Bishop, S. R., Lau, M., Shapiro, S., Carlson, L., Anderson, N. D.,Carmody, J., et al. Mindfulness: A proposed operational definition. Clinical Psychology-Science and Practice.2011; 18(3): 215-231.

11.Praissman S. Mindfulness-based stress reduction: a literature review and clinician's guide. J Am Acad Nurse Pract 2008; 20(4): 212-6.

12.Carlson LE. Mindfulness-based interventions for physical conditions: a narrative review evaluating levels of evidence. ISRN Psychiatry 2012; 2012:651583.

13. Segal ZV, Williams MG, Teasdale JD. Mindfulness Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse. Psychother Res. 2003; 13(1): 123-5.

14.Lauche R, Cramer H, Dobos G, Langhorst J, Schmidt S. A systematic review and meta-analysis of mindfulness-based stress reduction for the fibromyalgia syndrome. J Psychosom Res 2013; 75(6): 500-10.

15.Lakhan, S.E.,Schofield. Mindfulness-based therapies in the treatment of somatization disorders: a systematic review and meta-analysis. PLoS One 2013; 8(8):e71834.

16.Abbott, Whear, Rodgers LR, Bethel A, Thompson Coon J. Effectiveness of mindfulness-based stress reduction and mindfulness based cognitive therapy in vascular disease: A systematic review and meta-analysis of randomised controlled trials. J Psychosom Res 2014; 76(5): 341-51.

17.Strauss C, Cavanagh K, Oliver A, Pettman D. Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials. PLoS One 2014; 24;9(4).

18.Klainin-Yobas P, Cho MA, Creedy D. Efficacy of mindfulness-based interventions on depressive symptoms among people with mental disorders: a meta-analysis. Int J Nurs Stud, 2012; 49(1): 109-21.

19.Cramer H, Lauche R, Paul A, Dobos G. Mindfulness-based stress reduction for breast cancer-a systematic review and meta-analysis.Curr Oncol. 2012; 19(5): e343-52.

20.Zainal NZ, Booth S, Huppert FA. The efficacy of mindfulness-based stress reduction on mental health of breast cancer patients: a meta-analysis. Psychooncology, 2013; 22(7): 1457-65.

21.Musial F1, Büssing A, Heusser P, Choi KE, Ostermann T. Mindfulness-based stress reduction for integrative cancer care: a summary of evidence. Forsch Komplementmed, 2011; 18(4): 192-202.

22.Ledesma D, Kumano H. Mindfulness-based stress reduction and cancer: a meta-analysis. Psychooncology 2009; 18(6): 571-9.

23.Smith JE1, Richardson J, Hoffman C, Pilkington K. Mindfulness-Based Stress Reduction as supportive therapy in cancer care: systematic review. J Adv Nurs 2005; 52(3): 315-27.

24.Matchim Y, Armer JM, Stewart BR. Mindfulness-based stress reduction among breast cancer survivors: a literature review and discussion. Oncol Nurs Forum 2011; 38(2): E61-71.

25.Cramer H, Haller H, Lauche R, Dobos G. Mindfulness-based stress reduction for low back pain. A systematic review. BMC Complement Altern Med 2012;12: 162.

26.Chiesa A, Serretti A. Mindfulness based cognitive therapy for psychiatric disorders: a systematic review and meta-analysis. Psychiatry Res 2011; 187(3): 441-53. 27.Shiralkar MT1, Harris TB, Eddins-Folensbee FF, Coverdale JH. A systematic review of stress-management programs for medical students. Acad Psychiatry 2013; 37(3): 158-64.

28.Raab K. Mindfulness, self-compassion, and empathy among health care professionals: a review of the literature. J Health Care Chaplain 2014; 20(3): 95-108.

29.Higgins JPT, Altman DG. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.0.2 (updated September 2009). The Cochrane Collaboration 2009.

30.Higgins JPT, Altman DG. Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.0.2 (updated September 2009). The Cochrane Collaboration 2009)

31.Robinson FP, Mathews HL, Witek-Janusek L. Psycho-endocrine-immune response to mindfulness-based stress reduction in individuals infected with the human immunodeficiency virus: a quasiexperimental study. J Altern Complement Med 2003; 9(5): 683-94.

32.Creswell JD, Myers HF, Cole SW, Irwin MR. Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: a small randomized controlled trial. Brain Behav Immun 2009; 23(2): 184-8.

33.Gayner B, Esplen MJ, DeRoche P, Wong J, Bishop S, Kavanagh L, Butler K. A randomized controlled trial of mindfulness-based stress reduction to manage affective symptoms and improve quality of life in gay men living with HIV. J Behav Med 2012; 35(3): 272-85.

34.Duncan LG, Moskowitz JT, Neilands TB, Dilworth SE, Hecht FM, Johnson MO. Mindfulness-based stress reduction for HIV treatment side effects: a randomized, wait-list controlled trial. J Pain Symptom Manage 2012; 43(2): 161-71.

35.SeyedAlinaghi S, Jam S, Foroughi M, Imani A, Mohraz M, Djavid GE, et al. Randomized controlled trial of mindfulness-based stress reduction delivered to human immunodeficiency virus-positive patients in Iran: effects on CD4+ T lymphocyte count and medical and psychological symptoms. Psychosom Med 2012; 74(6): 620-7.

36.Weston E, Moran P, Acree M, Moskowitz J, Kemeny M, Elissa E, et al. 0A02.02. Effect of MBSR and psychological state on inflammatory markers in HIV positive adults. BMC Complement Altern Med 2012;12 (Suppl 1): 06.

37.Gonzalez-Garcia M, Ferrer MJ, Borras X, Muñoz-Moreno JA, Miranda C, Puig J, et al. Effectiveness of Mindfulness-Based Cognitive Therapy on the Quality of Life, Emotional Status, and CD4 Cell Count of Patients Aging with HIV Infection. AIDS Behav 2013 Sep 28. [Epub ahead of print]

38.Bohlmeijer E1, Prenger R, Taal E, Cuijpers P. The effects of mindfulness-based stress reduction therapy on mental health of adults with a chronic medical disease: a meta-analysis. J Psychosom Res, 2010; 68(6): 539-44.

39.Fjorback LO, Arendt M, Ornb E, Fink P, Walach H. Mindfulness-based stress reduction and

mindfulness-based cognitive therapy: a systematic review of randomized controlled trials. Acta Psychiatr Scand 2011; 124(2): 102-19.

40.Lengacher CA, Reich RR, Kip KE, Barta M, Ramesar S, Paterson CL, et al., Influence of Mindfulness-Based Stress Reduction (MBSR) on Telomerase Activity in Women With Breast Cancer (BC). Biol Res Nurs. 2014; 16(4): 438-47.

41. Matousek RH, Pruessner JC, and Dobkin PL. Changes in the cortisol awakening response (CAR) following participation in mindfulness-based stress reduction in women who completed treatment for breast cancer. Complement Ther Clin Pract 2011; 17(2): 65-70.

42.Lengacher CA, Kip KE, Post-White , Fitzgerald S. Lymphocyte recovery after breast cancer treatment and mindfulness-based stress reduction (MBSR) therapy. Biol Res Nurs 2013; 15(1): 37-47.

43.Gallegos AM, Hoerger M, Talbot NL, Krasner MS, Knight JM, Moynihan JA, et al.Toward identifying the effects of the specific components of Mindfulness-Based Stress Reduction on biologic and emotional outcomes among older adults. J Altern Complement Med.2013; 19(10): 787-92

44.Hoerger M, Talbot NL, Krasner MS. Toward identifying the effects of the specific components of Mindfulness-Based Stress Reduction on biologic and emotional outcomes among older adults. J Altern Complement Med 2013; 19(10): 787-92.

45.Jam S, Imani AH, Foroughi M, SeyedAlinaghi S, Koochak HE, Mohraz M. The effects of mindfulness-based stress reduction (MBSR) program in Iranian HIV/AIDS patients: a pilot study. Acta Med Iran 2010; 48(2): 101-6.

46.Sibinga EM, Stewart M, Magyari T, Welsh CK, Hutton N, Ellen JM. Mindfulness-based stress reduction for HIV-infected youth: A pilot study. Explore-the Journal Of Science And Healing 2008;4(1): 36-37.

47.Reich RR, Lengacher CA, Kip KE, Shivers SC, Schell MJ, Shelton MM, Widen RH, et al. Baseline Immune Biomarkers as Predictors of MBSR(BC) Treatment Success in Off-Treatment Breast Cancer Patients.Biol Res Nurs. 2014; 16(4): 429-37 .

48.Cohn M A,Epel E S, Moskowitz J T, Moran P.P., Acree M, Folkman S. High adherence enhances effects of mindfulness-based stress reduction. Psychosomatic Medicine 2011; 73(3): A63-4.

Table. Characteristics of the included studies

Design

Participants

Follow-

up (months)

Outcomes and tools

Findings

F. Patrie Robinson, et al, 2003 USA [31]

34 (32 males, 2 females), with a mean age of 43.08 + 6.07 years in the MBI group and 36.10 ±8.03 years in the control group

MBSR: 8 consecutive weekly sessions, lasting 2.5 h each, 1 full-day (8 hour) session, and individual pre-test and post program interviews; daily practice sS 45mins

© Perceived stress: PSS; © Mood States: POMS;

(3) Functional assessment: FAHI;

(4) Immune response: NK cell activity; RANTES; SDF-1

© Endocrine response: DHEAS; Cortisol; Cortisol/DHEAS

© Significant differences between groups regarding NK cell activity and numbers at 8 weeks; © No significant difference between groups regarding perceived stress, mood states, endocrine, or functional health variables at 8 weeks.

J. David Creswell, et al. 2009 USA [32]

Gayner B, et al 2012 Canada. [33]

Duncan I: i. et al. 2012 USA [34]

SeyedAlinag Iii S, et al., et al. 2012 Iran [35]

Weston E. et al. 2012 USA [36]

48 (43 males, 5 females), with a mean age of 40 + RCT 9 years in the MBI group and 42 +11 years in the control group

117 HIV gay men with an age range of 25-64 years

76 (64 males, 12 females), with a mean age of 47.9 + 6.8 years in RCT the MBI group and 48.2 + 9.1 years in the control group

171 (118 males, 53 females), with a mean age of 34.7+6.1 years in the MBI group and 45.6 + 6.9 years in the control group

132 HIV+adults (71 MBSR, 61 control) with CD4+ counts > 250 cells/jiL.

MBSR: 8 weekly 2 hour group sessions, a day-long retreat in the 7 th week; daily home mindfulness meditation practice.

MBSR consisting of eight 3-h weekly sessions and a day-long retreat with about an hour or more of homework per day, 6 days per week.

A standardized series of 8 weekly sessions of 2.5 to 3 hours; daily home assignments of mindfulness practice

MBSR is an eight-week group-based course in mindfulness meditation, and is described in the original MBSR manual

Control seminar: 1-day seminar

3, 6, 9, 12

© CD4 cell counts and HIV-RNA viral load;

© MBSR treatment adherence;

© Distress: IES; © Anxiety & depressive: HADS, (3) Positive affect and negative affects: PANAS; @ Mindfulness: TMS

© Side effects: AIDS Clinical

Trials Group symptom checklist;

© Adherence to ART;

(3) Depression: BDI

© Perceived stress: PSS

(5) Positive and negative affect:

PANAS;

© Mindfulness: FFMQ

© CD4 count; © Physical

Symptomatology: MSCL37; ©Mental health: SCL-90R

High sensitivity C-reactive protein (hsCRP); D-dimer

(D A significant difference between groups regarding CD4 cell counts; © No significant effects on HIV RNA.

(D A significant reduction in scores on the IES avoidance sub-scale; (2) A significant difference between groups in positive effects at 8 week and 6 month follow-up evaluations ©No significant difference in depression, anxiety, and the IES intrusion sub-scale scores between groups; (D A significant increase of mindfulness among participants in the intervention group at the 8-week and 6 month follow-up evaluations.

(D MBSR reduced both the frequency of symptoms attributable to ART and the distress related to HIV side effects; (2) No significant differences between groups regarding adherence, perceived stress, depression, positive and negative affect, and mindfulness.

(D A significant difference in CD4+counts between groups at 8 weeks, 3 months, 6 months and 9 months;

(2) A significant difference in Physical Symptomatology between groups at 8 weeks, 3 months, 6 months, and 12 months;

(3) A significant difference in the mental health of groups at 8 weeks, 3 months, 6 months, 9 months, and 12 months;

No effect on hsCRP or D-dimer levels at 3 or 12 months (p > 0.10)

GonzalezGarcia M, et al. 2013 Spain [37]

40 HIV infected participants (20 males, 20 females), with a mean age of 49.4+5.1 years

MBCT: 2.5 h per week over 8 weeks A minimum of 45 min/day and 6 days/week

© CD4 cell counts and HIV-RNA 1 load;

(2) Perceived stress: PSS-10;

(3) Depression: BDI-II © Anxiety: BAI

(5) Quality of life: NHP; © Adherence to cART, healthy diet, and smoking secession;

© A significant difference between groups regarding CD4 cell counts at week 20.© A significant difference between groups regarding stress, depression, anxiety, and quality of life at weeks 8 and 20. © No significant difference between groups regarding the level of HIV-RNA, adherence to cART, eating a healthy diet or smoking at weeks 8 and 20.

Note: Mindfulness-based Stress Reduction (MBSR); Mindfulness-based Cognitive Therapy (MBCT); Treatment-As-Usual (TAU); a wait-list control (WLC); antiretroviral therapy (ART); Education and Support (ESC); The Impact of Event Scale (IES); The Hospital Anxiety and Depression Scale (HADS); The Positive and Negative Affect Schedule (PANAS); The Toronto Mindfulness Scale (TMS); Nottingham Health Profile (NHP); Perceived Stress Scale (PSS-10); Beck Depression Inventory (BDI-II); Beck Anxiety Inventory (BAI); Five Factor Mindfulness Questionnaire (FFMQ); The Medical Symptom Checklist (MSCL (37); The Symptom Checklist-90-Revised (SCL-90R (41)

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Figure 2. Risk of bias for included studies.

Control

Std. Mean Difference

Sludv or Subgroup

Mean 5D Total Mean SD Total Weiobt IV. Random. 95% CI

1.1.1 MBSR VS Control

Duncan 2012 18.26 7.6 34 20.53 6.65

Gayner 2012 24.6 16.3 78 26.4 16.8

Robinson 2003 15.87 7.60 24 16.11 7.47

Subtotal (95% CI) 136

Heterogeneity: Tau2 = 0.00; Chi2 = 0.56, df = 2 (P = 0.76); I2; Test for overall effect: Z = 1.15 (P = 0.25)

1.1.2 MBCT VS Control

Gonzalez-Garcia 2013 13.4 7.4 19 21 5.1 Subtotal (95% CI) 19

Heterogeneity: Not applicable Test for overall effect: Z = 3.36 (P = 0.0008}

Total (95% CI) 155 100 100.0%

Heterogeneity: Tau2 = 0.12; Chi2 = 7.75, df = 3 (P = 0.05); I2 = 61% Test for overall effect: Z = 1.65 (P = 0.10)

Test for subarouo differences: Chi2 = 7,19. df = 1 (P = 0.007). Is = 86.1 %

31 39 10 80

27.7% 31.9% 19.4% 79.1%

20.9% 20.9%

-0.31 [-0.80, 0.18] -0.11 [-0,49. 0.28] -0.03 [-0.77, 0.71] -0.16 [-0.44, 0.12]

-1.18[-1.86,-0.49] -1.18 [-1.86, -0.49]

-0.37 [-0.82, 0.07]

-10 12 Favours [MBI] Favours [control]

Figure 3. Forest plot showing the short-term effects of MBSR/MBCR on stress (8 weeks)

Std. Mean Difference

stuav or ^uaarouD mean 1.2.2 MBSR VS Control au I otai ivican au I otai weipnt iv. Kanaom. a37o iv. rcanac m. yo /p I^I

Duncan 2012 18.24 6.66 37 21.06 8.32 34 35.5% -0.37 [-0.84. 0.10]

Gayner 2012 22.7 16.2 78 30,3 18.7 39 37.0% ■0.44 [-0.83. -0,05] ■

Subtotal (95% CI) 115 73 72.5% -0.41 [-0.71, -0.11] ♦

Heterogeneity: Tau2 = 0.00; Chi2 0.05, df = 1 (P - 0.82); I2 = 0%

Test for overall effect: Z = 2.71 (P = 0.007)

1.2.3 MBCR VS Control

Gonzalez-Garcia 2013 10.9 5.5 15 21.6 5 20 27.5% -2 00 [-2.84, -1.17]

Subtotal (95% CI) 15 20 27.5% -2.00 [-2.84, -1.17] -

Heterogeneity: Not applicable

Test for overall effect: Z = 4.71 (P < 0.00001 )

Total (95% CI) 130 93 100.0% -0.85 [-1.61. -0.0S] -1-1- -1-1-

Test for overall effect: Z = 2.17 (P = 0.03) Test for subarouD differences: Chi2 = 12.35. df =

1 (P = 0.0004). I2 = 91.9%

-2-1012 Favours [experimental] Favours [control]

Figure 4. Forest plot showing the short-term effects of MBSR/MBCR on stress (6 months)

Control

std. Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV. Random. 95% CI

1.2.1 MBSR VS Control

Duncan 2012 15.71 11.25 34 17.47 11.08 31

Gayner2012 7.1 4 78 8.1 3.5 39

Subtotal (95% CI) 112 70

Heterogeneity: Tau= = 0.00; Chi' = 0.11, df = 1 (P = 0.75); I' = 0% Test for overall effect: Z = 1.42 (P = 0.16)

1.2.2 MBCT VS Control

Gonzalez-Garcia 2013 10.1 9.3

Subtotal (95% CI)

Heterogeneity: Not applicable

Test for overall effect: Z = 2.47{P = 0.01)

19.9 13.4

33.4% 45.2% 78.7%

21.3% 21.3%

Total (95% CI) 131

Heterogeneity: Tau2 = 0.03; Chi1 - 2.83, df = 2 (P = 0.24); I2 = 29% Test for overall effect: Z = 2.01 (P = 0.04)

Test for suborauD differences: Chi2 = 2,73. df = 1 (P = 0.10V Is = 63.3%

-0.16 [-0.64, 0.33] -0.26 [-0.64, 0.13] -0.22 [-0.52, 0.08]

-0.83 [-1.49,-0.17] -0.83 [-1.49,-0.17]

90 100.0% -0.35 [-0.68, -0.01]

-1 -0.5 0 0.5 1

Favours [experimental] Favours [control]

Figure 5. Forest plot showing effects of MBSR/MBCR on depression (8 weeks)

Study or Subgroup

MBI Control Std. Mean Difference

Mean SD Total Mean SD Total Weight IV. Random. 95% CI

1.4.2 MBSR VS Control

Duncan 2012 14.25 9.27 37 19.35 14.18 34

Gayner 2012 7 4.3 78 8 4 39

Subtotal (95% CI) 115 73

Heterogeneity: Tau2 = 0.00; Chi» = 0.37. df = 1 (P = 0.54); I2 = 0% Test for overall effect: Z = 2.05 (P = 0.04)

1.4.3 MBCR vs control

Gonzalez-Garcia 2013 7.8 6.2 15 Subtotal (95% CI) 15

Heterogeneity: Not applicable Test for overall effect: Z = 2.79 (P = 0.005)

35.7% 43.2% 78.9%

21.1% 21.1%

Total (95% ci)

Heterogeneity: Tau2 = 0.05; Ch Test for overall effect: Z = 2.37 (P = 0.02) Test for suborouD differences: Chi2 = 3.20. df

130 93 100.0%

3.57, df = 2 (P - 0.17); P = 44%

-0.42 [-0.80, 0.05] -0.24 [-0.62, 0.15] -0.31 [-0.61,-0.01]

-1 02 [-1.74, -0.30] -1.02 [-1.74, -0.30]

-0.47 [-0.86, -0.08]

1 (p = 0.07). i2 = 68.8%

-2-1012 Favours [experimental] Favours [control]

Figure 6. Forest plot showing effects of MBSR/MBCR on depression (6 months)

Study Of Subgroup

MB! Control Std. Mean Difference Mean_SD Total Mean_SD Total Weight_IV. Random, 95% CI

1.11.3 active control Creswell 2009 SeyedAlinaghi 2012 Subtotal (95% CI) Heterogeneity: Tau2 =

10 5 33 -185 25.43 189.19 85 2.53 118

11.23; Chia = 58.13, df = 1 (P

Total (95% CI)

Heterogeneity: Tan2 = 2,80; Chi2 = 58.59, df = Test for overall effect; Z = 1.63 (P = 0.10) Test for subarouo differences: Chi2 = 0.92. df

70.5 15 183,72 86 101

0.00001); I2 = 98%

31.1% 34.9% 66.0%

Test tor overall effect: 2 = 1.04 (P = 0.30) 1.11,4 inactive control

Gonzalez-Garcia 2013 59 190.9 19 Subtotal (95% CI) 19

Heterogeneity: Not applicable

Test for overall effect; Z = 0,52 (P = 0.60)

23 230,86

20 34,0% 20 34.0%

2 (P< 0.00001); l2 =

100.0%

4.90 [3.71, 6.10] 0.12 [-0.18, 0.42] 2.48 [-2.21, 7.16]

0.17 [-0,46, 0.80] 0.17 [-0.46, 0.80]

1.62 [-0.32, 3.57]

• 1 (P = 0.341 la = 0%

-4 -2 0 2 4 MBI [experimental] Favours [control]

Figure 7. Forest plot showing effects of MBI on CD4+ counts at 8 weeks

Experimental

Control

Std. Mean Difference

Std. Mean Difference

atuayorsuoqroup mean ou lotai 1,12.1 active group mean -0.67 sli i oiai vveigm 62.2% iv. rcanaom. »siti u 0.11 [-0.19,0.41] iv. rcancic m. ss7o u ■

SeyedAlinaghi 2012 20,51 182,62 85 188.66 86

Subtotal (95% CI) 85 86 62.2% 0.11 [-0.19, 0.41J

Heterogeneity: Not applicable

Test for overall effect: Z = 0.74 (P = 0.46)

1.122 inactive group

Gonzalez-Garcla 2013 126 197 15 -49 243.1 20 37.8% 0.76 [0.07,1.46] -1'-

Subtotal (95% CI) 15 20 37.8% 0.76 [0.07,1.46]

Heterogeneity: Not applicable

Test for overall effect: Z = 2.14;P = 0.03)

Total (95% CI) 100 t-,, iz — n *t q- oh;; - n m At - i - n nm 106 - EAO/. 100,0% 0,36 [-0.26, 0.97] H-f- -1-1-

Test for overall effect: Z = 1.14 (P = 0.25) Test for subarouD differences: Chi2 = 2.81. df =

1 IP - 0.09). I! = 64.4%

-1 -0.5 0 0.5 1 Favours [experimental] Favours [control]

Figure 8. Forest plot showing effects of MBI on CD4+counts at 6 months