Severe mental illness at ART initiation is associated with worse retention in care among HIV-infected Ugandan adults

Authors


Corresponding Author Jean B. Nachega, Department of Medicine and Centre for Infectious Diseases, Faculty of Health Sciences, Stellenbosch University; Francie van Zijl Drive, Tygerberg Campus, Clinical Block, 3rd Floor, Room 3149; Cape Town, South Africa. Tel.: +27 938 9119; Fax: +27 938 9870; E-mail: jnachega@sun.ac.za or jnachega@jhsph.edu

Abstract

Objective

The impact of severe mental illness (SMI) on retention in HIV care remains uncertain. We aimed to measure the association between SMI at antiretroviral therapy (ART) initiation and subsequent retention in care in HIV-infected Ugandan adults.

Method

We conducted cohort study of 773 patients who initiated ART between January 2005 and July 2009 at the Butabika HIV clinic in Kampala, Uganda. SMI was defined as any clinically diagnosed organic brain syndrome, affective disorder or psychotic disorder. We used Kaplan–Meier and Cox proportional hazards analysis to evaluate the association between SMI and retention in care.

Results

The prevalence of SMI at ART initiation was 23%. Patients with SMI at baseline were similar to those without SMI in terms of age (median [IQR]: 35 [28–40] vs. 35 [30–40], P = 0.03), sex (36% vs. 35% female, P = 0.86) and baseline CD4+ T-cell count (112 [54–175] vs. 120 [48–187] cells/mm3, P = 0.86). At 12 months after ART initiation, Kaplan–Meier estimates of continuous retention in care were 65% (95% confidence interval, CI: 31–39%) among patients without SMI, vs. 47% (95% CI: 39–55%) among those with SMI (P < 0.001). All-cause mortality in the two groups was similar: 1.2% vs. 2.0% (P > 0.05). In multivariable analysis, the only baseline variable independently associated with breakage of continuous care was SMI (HR = 1.58, 95% CI: 1.06─2.33).

Conclusions

Severe mental illness at ART initiation is associated with worse retention in HIV care in this urban Ugandan referral hospital. As ART is scaled up across sub-Saharan Africa, greater attention must be paid to the burden of mental illness and its impact on retention in care.

Abstract

Objectif

L'impact de la maladie mentale sévère (MMS) sur la rétention dans les soins du VIH reste incertain. Nous avons cherché à mesurer l'association entre la MMS à l'initiation de la thérapie antirétrovirale (ART) et la rétention ultérieure dans les soins chez les adultes ougandais infectés par le VIH.

Méthode

Nous avons mené une étude de cohorte sur 773 patients qui ont commencé l’ART entre janvier 2005 et juillet 2009 à la clinique VIH de Butabika à Kampala, en Ouganda. La MMS a été définie comme tout syndrome cérébral organique cliniquement diagnostiqué, le trouble affectif ou psychotique. Nous avons utilisé l'analyse des risques proportionnels de Kaplan–Meier et Cox pour évaluer l'association entre la MMS et la rétention dans les soins.

Résultats

La prévalence de la MMS à l'initiation de l'ART était de 23%. Les patients atteints de MMS au départ étaient semblables à ceux sans MMS en termes d’âge [médiane (IQR): 35 (28–40) vs. 35 (30–40), P = 0,03], de sexe (36% contre 35% de femmes, P = 0,86) et de numération de base des cellules T CD4+ [112 (54–175) vs. 120 (48–187) cellules/mm3, P = 0,86]. A 12 mois après l'initiation de l'ART, les estimations de Kaplan–Meier pour la rétention continue dans les soins étaient de 65% (intervalle de confiance à 95% IC: 31-39%) chez les patients sans MMS, contre 47% (IC95%: 39–55%) chez ceux avec une MMS (P < 0,001). La mortalité toutes causes confondues dans les deux groupes était similaire: 1,2% vs. 2,0% (P > 0,05). Dans l'analyse multivariée, la seule variable de base indépendamment associée à une rupture de la continuité des soins était la MMS (HR = 1,58; IC95%: 1,06–2,33).

Conclusions

La MMS à l'initiation de l’ART est associée à une plus mauvaise rétention dans le traitement du VIH dans cet hôpital urbain de référence ougandais. Comme l’ART est déployée à travers l’Afrique subsaharienne, une plus grande attention devrait être accordée à la charge de morbidité de la maladie mentale et son impact sur la rétention dans les soins.

Abstract

Objetivo

El impacto de la enfermedad mental severa (EMS) sobre la retención dentro de los cuidados para VIH continúa siendo incierto. Buscábamos medir la asociación entre EMS y la iniciación de la terapia antirretroviral (TAR) y la retención subsecuente, en adultos infectados con VIH en Uganda.

Métodos

Hemos realizado un estudio de cohortes con 773 pacientes que iniciaron TAR entre Enero del 2005 y Julio del 2009 en la Clínica Butabika para VIH en Kampala, Uganda. La EMS se definió como un síndrome cerebral orgánico con diagnóstico clínico, desorden afectivo, o desorden psicótico. Utilizamos un análisis Kaplan-Meier y un modelo de riesgos proporcionales de Cox para evaluar la asociación entre EMS y la retención en los cuidados para VIH.

Resultados

La prevalencia de EMS al comienzo del TAR era del 23%. Los pacientes con EMS al comienzo del estudio eran similares a aquellos sin EMS en términos de edad (mediana [IQR]: 35 [28-40] vs. 35 [30-40], P = 0.03), sexo (36% vs. 35% mujer, P = 0.86), y conteo de células T CD4 +  al comienzo del estudio (112 [54-175] vs. 120 [48-187] células/mm3, P = 0.86). Doce meses después del inicio del TAR, los cálculos de Kaplan-Meier de retención continuada en los cuidados para VIH eran del 65% (95% intervalo de confianza, IC: 31-39%) entre pacientes sin EMS, versus 47% (95% IC: 39–55%) entre aquellos con EMS (P < 0.001). La mortalidad por cualquier causa en los dos grupos era similar: 1.2% vs. 2.0% (P > 0.05). En un análisis multivariado, la única variable presente al comienzo del estudio, independientemente asociada con el interrumpir los cuidados continuos era la EMS (HR = 1.58, IC 95%: 1.06–2.33).

Conclusiones

Una enfermedad mental severa al inicio del TAR estaba asociada con una peor retención en los cuidados para VIH en este hospital de referencia de Uganda. A medida que se extienda el TAR en África subsahariana, se deberá prestar una mayor atención a la carga de enfermedad mental y a su impacto sobre la retención de cuidados.

Mental illness is an important, and under-recognised, challenge to antiretroviral therapy (ART) adherence and retention in HIV care worldwide (Bhatia et al. 2011; Cournos et al. 2005; Chander et al. 2006; Nakimuli-Mpungu et al. 2012). High HIV prevalence rates among individuals with severe mental illness (SMI) have been reported in Uganda (Maling et al. 2011) and in the United States of America (USA) (Cournos & McKinnon 1997) with estimates as high as 18% and 22.9%, respectively. In the USA, interventions for SMI among people living with HIV have improved the quality of HIV care (Kelly & Kalichman 2002). In Uganda, HIV-positive individuals with SMI are often denied access to ART in general hospital settings and research studies (Rabkin 2008) because of presumed inability to adequately adhere or tolerate treatment. However, recent efforts to scale up ART and voluntary counselling and testing to all government regional and district hospitals have led to the establishment of an ART programme at the Butabika National Referral Mental Hospital, where many Ugandan adults now receive – for the first time – both HIV and mental health care in one location. To date, research in this patient population has focused mainly on describing the clinical presentation of different types of SMI among HIV-positive individuals initiating care (Nakimuli-Mpungu et al. 2006, 2008, 2009, 2010; Akena et al. 2010). In this study, we aimed to measure the association between SMI at ART initiation and subsequent retention in care.

We conducted a retrospective cohort analysis of 773 patients who consecutively were initiated ART between January 2005 and July 2009 at Butabika National Referral Mental hospital HIV clinic in Kampala, Uganda. We excluded patients who were younger than 18 years or had prior ART experience. This hospital's out-patient centre houses the mental health clinic and general medical clinics, including an HIV clinic that was established in 2004. In 2005, the clinic started its ART programme, which enrols individuals without mental illness from the surrounding urban community as well as those discharged from the mental hospital after receiving treatment for SMI, providing ART care free of charge.

Individuals are eligible for ART after clinical assessment if they have a CD4+ T-cell count of 200 or less, WHO clinical stage 3 or 4 disease or total lymphocyte count <1500 cells/mm3. First-line ART is a fixed-dose combination of stavudine, lamivudine and nevirapine. Demographic and clinical information including HIV symptoms, CD4+ T-cell counts, AIDS diagnosis and psychiatric diagnosis are obtained for all participants prior to ART initiation. Monthly clinic visits for regular assessments and medication refills are routine.

Data were collected as part of an ongoing retrospective medical chart review investigating patient characteristics, and clinical outcomes of individuals receiving care at the Butabika hospital Outpatient centre led by Dr. E. Nakimuli-Mpungu. Trained research assistants reviewed all medical charts of individuals who initiated ART in January 2005 through July 2009 and abstracted data on age at ART initiation, gender, marital status (single, married, widowed divorced/separated) and employment status (employed vs. unemployed), as well as number of HIV-related symptoms/opportunistic infections, baseline CD4+ T-cell counts and the presence of a psychiatric diagnosis. The date of ART initiation and the date of the last clinic visit were abstracted. Individuals whose last visit was more than 3 months prior to the date of administrative censoring were considered to have broken continuous HIV care.

Severe mental illness at the time of ART initiation was the primary exposure variable. SMI was defined as any clinically diagnosed bipolar disorder, chronic major depressive disorder with psychotic features, schizophrenia, schizoaffective disorder and other non-substance-abuse-related psychoses or another Axis I diagnosis with extensive history of prior hospitalisation (Schinnar et al. 1990). The primary outcome was continuous retention in care, defined as no breaks of >3 months between clinical visits. Analytical time was started at 3 months after ART initiation and continued for 12 months thereafter (i.e. to month 15 of total ART care). We used Kaplan–Meier and Cox proportional hazards analysis to evaluate the association between SMI and continuous retention in care. Multivariable models were adjusted for possible confounder variables such as age, sex, CD4+ T-cell count, HIV dementia and HIV wasting syndrome. For all analyses, P ≤ 0.05 was considered statistically significant. Data analysis was performed using stata 11 (Stata Corporation, College Station, TX, USA). This research study was approved by the Butabika hospital research committee, Makerere University College of health sciences research ethics committee and the Uganda National Council of Science and Technology.

The prevalence of SMI at ART initiation in this population was 23%. Patients with SMI at baseline were similar to those without SMI in terms of age (median [inter-quartile range]: 35 [28–40] vs. 35 [30–40], P = 0.03), sex (36% vs. 35% female, P = 0.86) and baseline CD4+ T-cell count (112 [54–175] vs. 120 [48–187] cells/mm3, P = 0.86) (Table 1). At 12 months after ART initiation, Kaplan–Meier estimates of continuous retention in care were 65% (95% confidence interval, CI: 61–69%) among patients without SMI, vs. 47% (95% CI: 39–55%) (P < 0.001) among those with SMI (Figure 1). Upon further inspection, the relative hazard associated with SMI was not constant over time. Specifically, SMI was associated with a relative hazard for breakage of care in the first 6 months of 1.70 (1.34–2.16), whereas among those who remained in care at 6 months, SMI had no additional effect on retention 1.14 (0.68–1.91) (Figure 2a,b). All-cause mortality in the two groups was similar: 1.2% vs. 2.0% (P > 0.05). In Cox multivariable analysis, the only baseline variable independently associated with worse retention in care was SMI (Table 2).

Figure 1.

Kaplan–Meier estimates of continuous retention in care among patients (without severe mental illness [SMI] vs. those with SMI).

Figure 2.

(a) Kaplan–Meier estimates of continuous retention in care among patients (Without severe mental illness [SMI] vs. those with SMI within 6 months). (b) Kaplan–Meier estimates of continuous retention in care among patients (without SMI vs. those with SMI after 6 months).

Table 1. Patient clinical and demographic characteristics at enrolment
VariableSMI (N = 181)No SMI (N = 592)Total (N = 773)P-value
  1. SMI, severe mental illness; ART, antiretroviral therapy.

Median (IQR) age (years)35 (28–40)35 (30–42)35 (30–41)0.03
Male, N (%)62 (34.8)209 (35.9)271 (35.6)0.86
ART initiation CD4 count112 (54–175)119 (48–187)118 (50–185)0.86
ART initiation year >2007, N (%)88 (48.6)197 (32.3)285 (36.9)<0.001
Patients in care at 12 months, N (%)35 (25.9)207 (48.4)242 (43.0)<0.001
HIV-related dementia, N (%)4 (2.2)2 (0.3)6 (0.8)0.03
HIV wasting syndrome, N (%)102 (56.4)217 (36.7)319 (41.3)<0.001
Toxoplasmosis, N (%)10 (5.5)19 (3.2)29 (3.8)0.18
Employed, N (%)37 (48.1)272 (75.4)309 (70.6)<0.001
Table 2. Factors associated with time to breakage of continuous HIV care
 Univariate HR (95% CI)P-valueMultivariate HR (95% CI)P-value
Age, years0.98 (0.97─1.00)0.080.98 (0.96─1.00)0.06
Male sex1.14 (0.81─1.61)0.461.20 (0.84─1.71)0.30
CD4 count <200 cells/μl0.84 (0.60─1.18)0.320.89 (0.63─1.25)0.50
Dementia3.10 (0.43─22.18)0.262.92 (0.37─22.67)0.31
Wasting syndrome1.16 (0.82─1.63)0.411.10 (0.77─1.58)0.59
Severe mental illness1.62 (1.11─2.37)0.011.58 (1.06─2.33)0.02

In this study of Ugandan adults initiating ART in an urban referral hospital, we found that SMI at ART initiation is associated with worse retention in HIV care, specifically over the first 6 months. This finding suggests that early interventions are needed for people living with HIV and SMI who are initiating ART.

Although individuals with SMI and HIV infection received care in the same setting, there are no targeted interventions designed to support and maintain these individuals in care. Randomised controlled trials have shown that combined mental health and ART adherence counselling interventions result in significant reductions in depressive symptoms, improved ART adherence and improved treatment outcomes. In developed countries, specialised programmes and services for serious mental illness and HIV-positive individuals have resulted in HIV care that is as good, and in some ways better than other HIV patients without SMI (Bogart et al. 2006; Safren et al. 2009; Gonzalez et al. 2011). Our findings show the need for such interventions in high-burden settings as well.

To our knowledge, this is the first study to report an association between SMI and retention in care in sub-Saharan Africa. The high SMI prevalence found in our study underscores the burden of mental health illness in HIV-infected individuals in resource-limited settings and a wake-up call for planning for mental health services (detection, management, etc.) in this setting. While informative, the limitations of our analysis include its retrospective design nature and possibility of unknown confounding factors that we were not able to adjust for in our multivariate model. In addition, given the referral nature of our recruiting site at Butabika Hospital, the high prevalence of SMI documented in this study population cannot be extrapolated to the general population of people living with HIV in Uganda.

The implications from this study are multiple. First, our results underscore the urgent need to improve screening and treatment of these mental health problems, particularly in light of the mounting evidence that they are associated with poor retention in care. Second, further research that examines the association between mental health and retention in care using prospective study designs is needed to confirm the causal direction of this association. Finally, a comprehensive approach that aim to address retention in care in ever growing ART programmes in Africa and other low- and middle-income countries, should include evaluation of targeted interventions that address mental health and their implementation if proven effective. One among other possible approaches could be integration of mental health care in ART programmes among peoples living with HIV/AIDS. In many HIV programmes worldwide, mental health services operate in isolation or in parallel with HIV treatment services.

In conclusion, SMI at ART initiation is associated with worse retention in HIV care in this urban Ugandan referral mental hospital. Greater attention must be paid to the burden of mental illness among people initiating ART in sub-Saharan Africa as ART is being scaled up.

Acknowledgements

This article was in part presented as a poster at the 19th Conference on Retroviruses and Opportunistic Infections. 5–9 March 2012. Seattle, WA, USA. Abstract# 1152. E N-M was supported by the Makerere University/SIDA-SAREC Faculty Research Grant; JN received support from the US NIH Medical Education Partnership Initiative, The European Developing Countries Clinical Trial Partnership and The Wellcome Trust Southern Africa Consortium for Research Excellence.

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