- Email: [email protected]
CBT for depression and drug adherence in HIV care
Comment
CBT for depression and drug adherence in HIV care Depression is the most prevalent neuropsychiatric disorder in people living with HIV/AIDS.1 Depression in this population is associated with multiple adverse events including poor adherence to treatment, risky sexual behaviour, and poor immune functioning.2,3 Despite the high prevalence of depression in people living with HIV/ AIDS, it is often unidentified and inadequately treated especially in low-income and middle-income countries (LMICs).4,5 Various treatment options including antidepressants and psychotherapies, such as cognitive behaviour therapy (CBT),6 are efficacious in treating mild-to-moderate forms of depression in people living with HIV/AIDS.7,8 In The Lancet HIV, Steven Safren and colleagues9 examine the efficacy of CBT for depression with adherence counselling (CBT-AD), information and supportive psychotherapy with adherence counselling (ISP-AD), and enhanced treatment as usual with adherence counselling (ETAU). Safren and colleagues show that CBT-AD is efficacious in improving adherence to antiretroviral drugs in people who are depressed and living with HIV/AIDS. A previous study10 by the same author had already shown the efficacy of CBT for the treatment of depression in people living with HIV/AIDS. As a treatment modality, CBT-AD has the potential to revolutionise mental health care in people living with HIV/AIDS because it tackles not only depression but also adherence to antiretroviral drugs. Previous studies focused solely on the treatment of depression and HIV in parallel, with little emphasis on the antiretroviral adherence, with the assumption that once depression has been treated adherence will improve. However, several studies11 show that parallel treatment of depression and HIV (without addressing adherence to antiretroviral drugs) improves symptoms of depression, but not HIV adherence. Adherence to antiretroviral drugs is of utmost importance in people living with HIV/AIDS. Over 90% adherence to antiretroviral drugs is needed for an HIV-positive person to be fully virally suppressed and to avoid the potential of a virological failure, which leads to AIDS.12 The need to achieve high levels of adherence to both antiretroviral drugs and antidepressants in people with depression who are living with HIV/AIDS cannot be overemphasised. www.thelancet.com/hiv Vol 3 November 2016
Safren and colleagues’ findings could particularly be useful in LMICs, especially in sub-Saharan Africa, where over two-thirds of people are living with HIV/AIDS,13 30% of whom might have depression.14 Particularly in sub-Saharan Africa, high numbers of patients and staff shortages severely hamper the delivery of depression care; CBT-AD is useful because it could be adopted for use in routine settings. Although one of the requirements for the delivery of CBT-AD to patients is rigorous training of health-care personnel, delivery by lay health-care workers in LMICs should be explored. Studies have already shown that the delivery of mental health care by lay health-care workers in HIV care settings in LMICs is feasible and associated with better clinical outcomes.15 Safren and colleagues’ findings are especially timely now that the public health benefits of treatment of depression are clearer than ever. As mentioned by the authors, the cost-effectiveness of this model of care needs to be investigated in LMICs where resources allocated for mental health care are meagre. Despite the interesting findings, this study was not without limitations. First, the recruitment of patients with residual symptoms of depression means that more studies are needed to examine the efficacy of CBT-AD for severe forms of depression. Second, CBT-AD was compared with ETAU, which is already an enhanced form of care. The limitation of this particular method is that even for such a well powered study, patients with mild forms of depression are likely to respond to ETAU, making it difficult to fully examine the efficacy of CBT-AD. Studies that compare CBT-AD with placebo are needed.
Published Online September 19, 2016 http://dx.doi.org/10.1016/ S2352-3018(16)30060-1 See Articles page e529
*Dickens Akena, Hillary Kuteesa, Racheal Alinaitwe Department of Psychiatry (DA, HK, RA), and Africa Centre for Systematic Reviews and Knowledge Translation (DA), Makerere University College of Health Sciences, Kampala, Uganda [email protected] We declare no competing interests. 1 2
3
Olatunji BO, Mimiaga MJ, O’Cleirigh C, Safren SA. Review of treatment studies of depression in HIV. Top HIV Med 2006; 14: 112–24. Wagner GJ, Ngo VK, Nakasujja N, Akena D, Aunon F, Musisi S. Impact of antidepressant therapy on cognitive aspects of work, condom use, and psychosocial well-being among HIV clients in Uganda. Int J Psychiatry Med 2014; 48: 155–66. Gonzalez JS, Batchelder AW, Psaros C, Safren SA. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr 2011; 58: 181–87.
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Collins PY, Holman AR, Freeman MC, Patel V. What is the relevance of mental health to HIV/AIDS care and treatment programs in developing countries? A systematic review. AIDS 2006; 20: 1571–82. Akena D, Stein DJ, Joska J. Does screening HIV-positive individuals in Uganda for major depressive disorder improve case detection rates and antidepressant prescription? AIDS Behav 2012; 17: 2802–07. Chibanda D, Cowan FM, Healy JL, Abas M, Lund C. Psychological interventions for common mental disorders for people living with HIV in low- and middleincome countries: systematic review. Trop Med Int Health 2015; 20: 830–39. Ngo VK, Wagner GJ, Nakasujja N, Dickens A, Aunon F, Musisi S. Effectiveness of antidepressants and predictors of treatment response for depressed HIV patients in Uganda. Int J STD AIDS 2015; 14: 998–1006. Himelhock S, Medoff DR. Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. AIDS Patient Care STDs 2005; 19: 813–22. Safren SA, Bedoya CA, O’Cleirigh C, et al. Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial. Lancet HIV 2016; published online Sept 19. http://dx.doi. org/10.1016/S2352-3018(16)30053-4.
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Safren SA, O’Cleirigh C, Tan JY, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol 2009; 28: 1–10. Tsai AC, Karasic DH, Hammer GP, et al. Directly observed antidepressant medication treatment and HIV outcomes among homeless and marginally housed HIV-positive adults: a randomized controlled trial. Am J Public Health 2013; 103: 308–15. Turner BJ. Adherence to antiretroviral therapy by human immunodeficiency virus-infected patients. J Infect Dis 2002; 185 (suppl 2): S143–51. Brandt R. The mental health of people living with HIV/AIDS in Africa: a systematic review. Afr J AIDS Res 2009, 8: 123–33. Nakimuli-Mpungu E, Bass JK, Alexandre P, et al. Depression, alcohol use and adherence to antiretroviral therapy in sub-Saharan Africa: a systematic review. AIDS Behav 2011; 15: 376–88. Wagner GJ, Ngo V, Goutam P, Glick P, Musisi S, Akena D. A structured protocol model of depression care versus clinical acumen: a cluster randomized trial of the effects on depression screening, diagnostic evaluation, and treatment uptake in Ugandan HIV clinics. PLoS One 2016; 11: e0153132.
Accelerating initiation of antiretroviral therapy Published Online August 26, 2016 http://dx.doi.org/10.1016/ S2352-3018(16)30152-7 See Articles page e539
e504
When programmes first started to provide antiretroviral therapy (ART) in resource-limited settings, availability of treatment was very restricted, and there were concerns that large-scale treatment provision without adequate adherence could lead to widespread HIV drug resistance.1 Decisions about starting ART were made with caution, applying multiple medical, social, and adherence-readiness criteria.2 Although many of these restrictive criteria were abandoned as treatment became simpler and more widely available, multiple lengthy counselling sessions before starting ART continue to be the norm, often resulting in substantial delays between establishment of eligibility and start of ART. However, the benefit of such sessions has not been clearly established,3 and multiple visits before starting treatment can result in patient losses to care and avoidable mortality.4,5 A better understanding of how quickly to start ART is particularly important now that all HIV-positive individuals are eligible for treatment.6 In The Lancet HIV, Gideon Amanyire and colleagues7 present the results of the START-ART trial, which provides important insights about how to speed up ART initiation. In this trial, 20 clinics in Uganda were randomly assigned in groups of five clinics every 6 months to receive a packaged intervention that included opinion-leader-led training of health-care workers, point-of-care CD4 cell count devices, and reputational incentives, with the aim of accelerating the speed and uptake of ART initiation. Treatment-naive,
HIV-infected adults visiting the clinics who were clinically eligible for ART during the study period were included in the study population. A greater proportion of patients in the intervention group started ART on the same day that eligibility was established (71% in the intervention group vs 18% in the control group) and by 2 weeks after eligibility (80% vs 38%), and this difference was maintained over time. Viral suppression at 12 months was also greater in the intervention group than in the control group after adjustment for missing data (85% vs 75%) and there were no differences in mortality or loss to follow-up. The trial investigators stress the importance of multicomponent interventions in effecting changes in health service delivery. However, many examples exist of single interventions leading to changes in programme performance, and the appropriateness of the particular package of interventions tested in the START-ART trial is questionable now that CD4 cell count is no longer required before starting ART. The START-ART trial adds important evidence that same-day initiation of ART can be implemented in routine programme settings, although evidence is mixed on the benefits of same-day start. Results of a randomised trial in South Africa showed that, overall, same-day start resulted in more patients on ART overall compared with usual care (three to five clinic visits), mainly because more people were lost to follow-up before ART initiation in the nonintervention group.8 After ART initiation, however, a greater proportion of people were lost to followup in the same-day start group, although the trial www.thelancet.com/hiv Vol 3 November 2016
CBT for depression and drug adherence in HIV care Depression is the most prevalent neuropsychiatric disorder in people living with HIV/AIDS.1 Depression in this population is associated with multiple adverse events including poor adherence to treatment, risky sexual behaviour, and poor immune functioning.2,3 Despite the high prevalence of depression in people living with HIV/ AIDS, it is often unidentified and inadequately treated especially in low-income and middle-income countries (LMICs).4,5 Various treatment options including antidepressants and psychotherapies, such as cognitive behaviour therapy (CBT),6 are efficacious in treating mild-to-moderate forms of depression in people living with HIV/AIDS.7,8 In The Lancet HIV, Steven Safren and colleagues9 examine the efficacy of CBT for depression with adherence counselling (CBT-AD), information and supportive psychotherapy with adherence counselling (ISP-AD), and enhanced treatment as usual with adherence counselling (ETAU). Safren and colleagues show that CBT-AD is efficacious in improving adherence to antiretroviral drugs in people who are depressed and living with HIV/AIDS. A previous study10 by the same author had already shown the efficacy of CBT for the treatment of depression in people living with HIV/AIDS. As a treatment modality, CBT-AD has the potential to revolutionise mental health care in people living with HIV/AIDS because it tackles not only depression but also adherence to antiretroviral drugs. Previous studies focused solely on the treatment of depression and HIV in parallel, with little emphasis on the antiretroviral adherence, with the assumption that once depression has been treated adherence will improve. However, several studies11 show that parallel treatment of depression and HIV (without addressing adherence to antiretroviral drugs) improves symptoms of depression, but not HIV adherence. Adherence to antiretroviral drugs is of utmost importance in people living with HIV/AIDS. Over 90% adherence to antiretroviral drugs is needed for an HIV-positive person to be fully virally suppressed and to avoid the potential of a virological failure, which leads to AIDS.12 The need to achieve high levels of adherence to both antiretroviral drugs and antidepressants in people with depression who are living with HIV/AIDS cannot be overemphasised. www.thelancet.com/hiv Vol 3 November 2016
Safren and colleagues’ findings could particularly be useful in LMICs, especially in sub-Saharan Africa, where over two-thirds of people are living with HIV/AIDS,13 30% of whom might have depression.14 Particularly in sub-Saharan Africa, high numbers of patients and staff shortages severely hamper the delivery of depression care; CBT-AD is useful because it could be adopted for use in routine settings. Although one of the requirements for the delivery of CBT-AD to patients is rigorous training of health-care personnel, delivery by lay health-care workers in LMICs should be explored. Studies have already shown that the delivery of mental health care by lay health-care workers in HIV care settings in LMICs is feasible and associated with better clinical outcomes.15 Safren and colleagues’ findings are especially timely now that the public health benefits of treatment of depression are clearer than ever. As mentioned by the authors, the cost-effectiveness of this model of care needs to be investigated in LMICs where resources allocated for mental health care are meagre. Despite the interesting findings, this study was not without limitations. First, the recruitment of patients with residual symptoms of depression means that more studies are needed to examine the efficacy of CBT-AD for severe forms of depression. Second, CBT-AD was compared with ETAU, which is already an enhanced form of care. The limitation of this particular method is that even for such a well powered study, patients with mild forms of depression are likely to respond to ETAU, making it difficult to fully examine the efficacy of CBT-AD. Studies that compare CBT-AD with placebo are needed.
Published Online September 19, 2016 http://dx.doi.org/10.1016/ S2352-3018(16)30060-1 See Articles page e529
*Dickens Akena, Hillary Kuteesa, Racheal Alinaitwe Department of Psychiatry (DA, HK, RA), and Africa Centre for Systematic Reviews and Knowledge Translation (DA), Makerere University College of Health Sciences, Kampala, Uganda [email protected] We declare no competing interests. 1 2
3
Olatunji BO, Mimiaga MJ, O’Cleirigh C, Safren SA. Review of treatment studies of depression in HIV. Top HIV Med 2006; 14: 112–24. Wagner GJ, Ngo VK, Nakasujja N, Akena D, Aunon F, Musisi S. Impact of antidepressant therapy on cognitive aspects of work, condom use, and psychosocial well-being among HIV clients in Uganda. Int J Psychiatry Med 2014; 48: 155–66. Gonzalez JS, Batchelder AW, Psaros C, Safren SA. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr 2011; 58: 181–87.
e503
Comment
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Collins PY, Holman AR, Freeman MC, Patel V. What is the relevance of mental health to HIV/AIDS care and treatment programs in developing countries? A systematic review. AIDS 2006; 20: 1571–82. Akena D, Stein DJ, Joska J. Does screening HIV-positive individuals in Uganda for major depressive disorder improve case detection rates and antidepressant prescription? AIDS Behav 2012; 17: 2802–07. Chibanda D, Cowan FM, Healy JL, Abas M, Lund C. Psychological interventions for common mental disorders for people living with HIV in low- and middleincome countries: systematic review. Trop Med Int Health 2015; 20: 830–39. Ngo VK, Wagner GJ, Nakasujja N, Dickens A, Aunon F, Musisi S. Effectiveness of antidepressants and predictors of treatment response for depressed HIV patients in Uganda. Int J STD AIDS 2015; 14: 998–1006. Himelhock S, Medoff DR. Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. AIDS Patient Care STDs 2005; 19: 813–22. Safren SA, Bedoya CA, O’Cleirigh C, et al. Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial. Lancet HIV 2016; published online Sept 19. http://dx.doi. org/10.1016/S2352-3018(16)30053-4.
10
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13 14
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Safren SA, O’Cleirigh C, Tan JY, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol 2009; 28: 1–10. Tsai AC, Karasic DH, Hammer GP, et al. Directly observed antidepressant medication treatment and HIV outcomes among homeless and marginally housed HIV-positive adults: a randomized controlled trial. Am J Public Health 2013; 103: 308–15. Turner BJ. Adherence to antiretroviral therapy by human immunodeficiency virus-infected patients. J Infect Dis 2002; 185 (suppl 2): S143–51. Brandt R. The mental health of people living with HIV/AIDS in Africa: a systematic review. Afr J AIDS Res 2009, 8: 123–33. Nakimuli-Mpungu E, Bass JK, Alexandre P, et al. Depression, alcohol use and adherence to antiretroviral therapy in sub-Saharan Africa: a systematic review. AIDS Behav 2011; 15: 376–88. Wagner GJ, Ngo V, Goutam P, Glick P, Musisi S, Akena D. A structured protocol model of depression care versus clinical acumen: a cluster randomized trial of the effects on depression screening, diagnostic evaluation, and treatment uptake in Ugandan HIV clinics. PLoS One 2016; 11: e0153132.
Accelerating initiation of antiretroviral therapy Published Online August 26, 2016 http://dx.doi.org/10.1016/ S2352-3018(16)30152-7 See Articles page e539
e504
When programmes first started to provide antiretroviral therapy (ART) in resource-limited settings, availability of treatment was very restricted, and there were concerns that large-scale treatment provision without adequate adherence could lead to widespread HIV drug resistance.1 Decisions about starting ART were made with caution, applying multiple medical, social, and adherence-readiness criteria.2 Although many of these restrictive criteria were abandoned as treatment became simpler and more widely available, multiple lengthy counselling sessions before starting ART continue to be the norm, often resulting in substantial delays between establishment of eligibility and start of ART. However, the benefit of such sessions has not been clearly established,3 and multiple visits before starting treatment can result in patient losses to care and avoidable mortality.4,5 A better understanding of how quickly to start ART is particularly important now that all HIV-positive individuals are eligible for treatment.6 In The Lancet HIV, Gideon Amanyire and colleagues7 present the results of the START-ART trial, which provides important insights about how to speed up ART initiation. In this trial, 20 clinics in Uganda were randomly assigned in groups of five clinics every 6 months to receive a packaged intervention that included opinion-leader-led training of health-care workers, point-of-care CD4 cell count devices, and reputational incentives, with the aim of accelerating the speed and uptake of ART initiation. Treatment-naive,
HIV-infected adults visiting the clinics who were clinically eligible for ART during the study period were included in the study population. A greater proportion of patients in the intervention group started ART on the same day that eligibility was established (71% in the intervention group vs 18% in the control group) and by 2 weeks after eligibility (80% vs 38%), and this difference was maintained over time. Viral suppression at 12 months was also greater in the intervention group than in the control group after adjustment for missing data (85% vs 75%) and there were no differences in mortality or loss to follow-up. The trial investigators stress the importance of multicomponent interventions in effecting changes in health service delivery. However, many examples exist of single interventions leading to changes in programme performance, and the appropriateness of the particular package of interventions tested in the START-ART trial is questionable now that CD4 cell count is no longer required before starting ART. The START-ART trial adds important evidence that same-day initiation of ART can be implemented in routine programme settings, although evidence is mixed on the benefits of same-day start. Results of a randomised trial in South Africa showed that, overall, same-day start resulted in more patients on ART overall compared with usual care (three to five clinic visits), mainly because more people were lost to follow-up before ART initiation in the nonintervention group.8 After ART initiation, however, a greater proportion of people were lost to followup in the same-day start group, although the trial www.thelancet.com/hiv Vol 3 November 2016