Effect of suicidality on clinical and behavioural outcomes in HIV positive adults in Uganda
Abstract
Suicidality is a risk of a person committing suicide often characterized by suicidal ideation, intent or attempts. Despite the high burden of suicidality among individuals living with HIV and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4 counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV Medications). Cross-sectional investigations of these associations are often complicated by bidirectional causal relationships and hence the need for longitudinal study designs.
We
conducted a cohort study to determine the impact of suicidality on clinical and behavioural outcomes among adults living with HIV/AIDS in Uganda.
We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda.
Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to determine the relationship between suicidality and indices of HIV outcomes.
Majority of the participants were female and the participant mean age was 35 years. Most of them (73%) had primary or no formal education. The proportion of participants with suicidality decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the investigated clinical and behavioural outcomes, baseline suicidality only had a negative impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI 2.45–27.71, p>0.01) times higher for participants with suicidality compared to those without suicidality. The following outcomes were not significantly impacted by baseline suicidality: HIV clinical stage, CD4 count and risky sexual behaviour.
The fact that baseline suicidality significantly negatively impacted ART adherence calls for the incorporation of psychosocial interventions to target indices of psychological distress such as suicidality to improve HIV related outcomes.
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RESEARCH ARTICLE
Effect of suicidality on clinical and behavioural
outcomes in HIV positive adults in Uganda
Godfrey Zari RukundoID
1
*, Jonathan Levin
2
, Richard Stephen Mpango
3,4
, Vikram Patel
5
,
Eugene Kinyanda
3,6
1Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, Uganda, 2School of
Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,
3Mental Health Project, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda, 4Department of
Mental Health, School of Health Sciences, Soroti University, Soroti, Uganda, 5Department of Global Health
and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America,
6Department of Psychiatry, Makerere College of Health Sciences, Kampala, Uganda
*grukundo@must.ac.ug
Abstract
Introduction
Suicidality is a risk of a person committing suicide often characterized by suicidal ideation,
intent or attempts. Despite the high burden of suicidality among individuals living with HIV
and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4
counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV
Medications). Cross-sectional investigations of these associations are often complicated by
bidirectional causal relationships and hence the need for longitudinal study designs. We
conducted a cohort study to determine the impact of suicidality on clinical and behavioural
outcomes among adults living with HIV/AIDS in Uganda.
Materials and methods
We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda.
Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and
discrete time survival models were used to determine the relationship between suicidality
and indices of HIV outcomes.
Results
Majority of the participants were female and the participant mean age was 35 years. Most of
them (73%) had primary or no formal education. The proportion of participants with suicidal-
ity decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the
investigated clinical and behavioural outcomes, baseline suicidality only had a negative
impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95%
CI 2.45–27.71, p>0.01) times higher for participants with suicidality compared to those with-
out suicidality. The following outcomes were not significantly impacted by baseline suicidal-
ity: HIV clinical stage, CD4 count and risky sexual behaviour.
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OPEN ACCESS
Citation: Rukundo GZ, Levin J, Mpango RS, Patel
V, Kinyanda E (2021) Effect of suicidality on clinical
and behavioural outcomes in HIV positive adults in
Uganda. PLoS ONE 16(8): e0254830. https://doi.
org/10.1371/journal.pone.0254830
Editor: Orvalho Augusto, University of Washington,
UNITED STATES
Received: January 8, 2021
Accepted: July 5, 2021
Published: August 20, 2021
Copyright: This is an open access article, free of all
copyright, and may be freely reproduced,
distributed, transmitted, modified, built upon, or
otherwise used by anyone for any lawful purpose.
The work is made available under the Creative
Commons CC0 public domain dedication.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
files.
Funding: This study was funded by a senior
fellowship from the European & Developing
Countries Clinical Trials Partnership (EDCTP)
Project No. TA.2010.40200.011 to Eugene
Kinyanda. The funders had no role in study design,
data collection and analysis, decision to publish or
manuscript writing.
Competing interests: The authors have declared
that no competing interests exist.
Conclusions
The fact that baseline suicidality significantly negatively impacted ART adherence calls for
the incorporation of psychosocial interventions to target indices of psychological distress
such as suicidality to improve HIV related outcomes.
Introduction
Suicidal ideation and attempts often referred to as suicidality are major risk factors for future
completed suicide [1]. Apart from being a risk factor for suicide, suicidality also has negative
impact on the quality of life lived by the affected individuals and their families [2]. Individuals
with physical illnesses which are associated with shame, long suffering or pain, such as HIV/
AIDS, have a higher risk of depression and suicidality [3–5]. In a Ugandan cohort of individu-
als with HIV/AIDS, depression negatively impacted the clinical and behavioural outcomes of
HIV [6]. However, there is paucity of data on the impact of persistent suicidality (suicidal idea-
tion and attempts) on clinical outcomes (such as CD4 counts and WHO clinical stage of HIV)
and behavioural outcomes such as adherence to HIV medications and health seeking behav-
iour. Previous studies on suicidality in HIV/AIDS, have generally considered HIV related clin-
ical factors as predictors for suicide [7,8]. However, the relationship could be bidirectional,
with suicide worsening the clinical and behavioural outcomes in individuals living with HIV.
Cross-sectional investigations of these associations are often complicated by the bidirec-
tional causal relationships and hence the need for longitudinal study designs. We conducted a
cohort study to determine the impact of suicidality on clinical and behavioural outcomes
among adults living with HIV/AIDS in Uganda. The findings of this study will help in the
identification of possible intervention strategies such as integration of suicidality assessment
and management into routine HIV care.
Materials and methods
Study design and site
This was a prospective cohort study among adults living with HIV (PLWH), attending two
specialized HIV clinics, the semi-urban site clinic in Entebbe’ and the ‘predominantly rural
clinic in Masaka, run by The AIDS Support Organisation (TASO) in Uganda [9].’ The study
was conducted from May 2012 to December 2013. Data collection was undertaken at three
time points: baseline (when participants undertook their first study interview after enrolment
into the study) 6-months after the baseline assessment and 12-months after baseline assess-
ment. Initiation of ART was implemented by TASO independently of the study. At the time of
the study, national treatment guidelines for HIV-infected individuals recommended the initia-
tion of ART at a CD4 cell count of below 250 cells / μl. In addition, individuals initiating ART
were required to have identified an appropriate treatment supporter.
Sampling procedure
At the time of the study, TASO clinic in Entebbe had 7000 active clients of whom about 3000
were ART naïve while TASO clinic in Masaka had 6,000 active clients of whom about 2,500
were not on ART. This study aimed to enroll 1100 ART naïve HIV-infected adults from the
two clinics. The sample was selected by simple random sampling; 1100 at baseline, 1059 at six
months follow up and 1041 at 12 months follow up (Fig 1). In order to determine the effect of
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suicidality on clinical and behavioural outcomes, we aimed to detect an effect size of 0.15 with
the power of 90%, αof 0.05 (two sided), βof 0.1 [6]. To obtain the required sample from the
two HIV clinics, a sub-register of all active but HIV naïve clients was created. From these sub-
registers a random sample of ART naïve patients was recruited from each study clinic using a
table of random numbers until a combined total study sample of 1100 was obtained.
Risky sexual behavior was measured by at least one affirmative answer to the 5 questions on
sexual behaviour. The questions included: ‘in the last month, have you had sex with anyone
other than your regular partner?’ Among those who practiced high risk sexual behaviours ‘did
you always use condoms?’ ii) have you had sex in exchange for gifts/money? iii) Have you had
forced sex including rape? iv) Have you had sex with someone much older/younger than you?
v) Have you had sex with someone you had just met?)’.
The inclusion criteria for this study were: i) a person living with HIV/AIDS who was ART
naïve and registered with the outpatient clinic at either TASO Entebbe and TASO Masaka clin-
ics; ii) aged at least 18 years old at enrolment; iii) conversant in Luganda, the language in
which the study instruments were translated. Exclusion criteria were patients who were too
sick or unable to understand the study instruments, and those who had missed their most
recent scheduled clinic visit. Eligible participants (Fig 1) were recruited after they had provided
written informed consent after explanation of the study objectives and procedures. About 2%
of the selected patients could not be recruited into this study because of any one of the follow-
ing reasons: i) were already enrolled in another study or ii) refused to participate in the study
for any other reason.
Fig 1. Flow chart showing participant recruitment data collection tools. This figure shows the initial sample size of
1100 and the participants who were excluded and those who were lost to follow up at 6 months and at 12 months. Entries
for one participant were found to be incomplete and were not included in the final analysis which was done for 1099
instead of 1100 participants.
https://doi.org/10.1371/journal.pone.0254830.g001
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Individuals found to have significant psychiatric problems requiring specialist assessment
and management were referred to psychiatric departments/units nearest to the study sites.
The data collection tools consisted of structured and standardised locally translated psycho-
social assessment instruments, most of which have previously been used among persons living
with HIV (PLWH) in Uganda by this study group [10]. The study variables were: socio-demo-
graphic factors: these included study site, sex, age, highest educational attainment, marital sta-
tus, religion, occupation and socio-economic index (SES index) [10]. 2) Psychosocial factors
(coping style, negative life events and social support) were some of the variables in this study.
We considered mean scores for each of the three variables 3) Exposure variable (suicidality)
defined as having serious suicidal ideation and or suicidal attempt in the past twelve months
from the date of assessment as determined by the section on suicide in the Diagnostic Statisti-
cal Manual IV–based suicidality module of the Mini International Neuropsychiatric Interview
(M.I.N.I) [11]. Suicidality assessments were considered for each of the 3 time points and were
reported as a binary outcome with respondents reporting as either having suicidality or not
having suicidality. A diagnosis of suicidality was made if the respondent answered yes to the
question on suicidal ideation or the one on suicidal attempt or both questions. 4) Indices of
HIV related outcome measures: i) HIV disease progression [CD4 counts, WHO Clinical Stag-
ing criteria) [16]; ii) health seeking behaviour (number of visits to health facilities in last
month; iii) adherence to HIV medications [three day antiretroviral therapy pill count recall
[12,13]; and iv) risky sexual behaviour [6].
Statistical analysis
The impact of suicidality on the four HIV-related outcome domains (HIV disease progression,
adherence to HIV medications, health seeking behaviour and risky sexual behaviour) was
investigated using five outcome variables: i) CD4 count at visit 2 ii) Having experienced a
WHO stage 3 or 4 event at month 6 or month 12 iii) Having missed at least one dose of ART
medications in the three days prior to the interview iv) The time to the first visit to a health
facility-measure of health seeking behaviour and v) Having engaged in risky sexual behaviour.
Risky sexual behavior was measured by at least one affirmative answer to the 5 questions on
sexual behaviour. The questions included: ‘in the last month, have you had sex with anyone
other than your regular partner?’ Among those who practiced high risk sexual behaviours ‘did
you always use condoms?’ ii) have you had sex in exchange for gifts/money? iii) have you had
forced sex including rape?; iv) have you had sex with someone much older/younger than you?;
v) have you had sex with someone you had just met?)’. Entries for one participant were found
to be incomplete and were not included in the final analysis which was done for 1099 instead
of 1100 participants that were initially enrolled.
i) CD4 count at visit 2 (6 months) and visit 3 (12 months).Suicidality at baseline was used
as the exposure variable at month 6, whereas suicidality at month 6 was used as the exposure
variable at month 12. Multiple linear regression models were fitted with the use of robust stan-
dard errors to account for the correlation between CD4 counts within participants. The analy-
sis adjusted for study site, sex, age at baseline, visit (i.e. month 6 or month 12), and baseline
CD4 cell count as explanatory variables. Participants who initiated ART between baseline and
month 6 were excluded, whereas participants who initiated ART between month 6 and month
12 were included at month 6 but excluded at month 12. The measure of association for CD4
count is the difference in CD4 cell count (cells/mL) between participants with suicidality (at
the previous visit) and those without suicidality.
ii) Having experienced a WHO stage 3 or 4 event at month 6 or month 12 was also used to
measure the domain HIV disease progression. The time to the first WHO stage 3 or 4 event
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was analyzed using discrete time survival models [14]. Discrete time survival models were
used to investigate the time (6 months or 12 months) to the first WHO stage 3 or 4 event. The
primary exposure, suicidality, was lagged, that is, suicidality at baseline was used as the expo-
sure variable for a WHO stage 3 or 4 event at month 6 (characterized by weight loss of more
than 10%, chronic diarrhea for more than a month, fevers for more than a month, oral thrush,
oral hairy leucoplekia, TB within the last 1 year, and severe bacterial infections like pneumonia
and pyomyositis). The analysis adjusted for study site, sex, age, visit (ie, month 6 or month 12),
initiation of ART and baseline CD4 cell count as explanatory variables. Participants who initi-
ated ART before month 6 were excluded, whereas those who initiated ART between month 6
and month 12 were included at month 6 but excluded at month 12. Participants who had
already experienced a WHO stage 3 or 4 event at baseline were also excluded from the analysis.
The measure of association is the (adjusted) odds ratio for a WHO stage 3 or 4 event for partic-
ipants with suicidality (at the previous visit) compared with those without suicidality.
iii) Having missed at least one dose of ART medications in the 3 days before the interview
was used as a measure for the domain on adherence to HIV medication. Missing at least one
dose of ART at month 6 and month 12 was analyzed by fitting a multiple logistic regression
model to a “long” data set with up to 2 observations per participant; robust standard errors were
used to account for the correlation of responses within participants. In this case, the primary
exposure (suicidality) was not lagged, since the suicidality was evaluated over the 2 weeks before
the visit and missing at least one dose of ART was evaluated over the 3 days before the visit, so
we assumed that the exposure (suicidality) preceded the outcome (missing at least one dose of
ART). The analysis adjusted for study site, sex, age, visit (i.e. month 6 or month 12), and base-
line CD4 cell count as explanatory variables. The analysis was restricted to participants who ini-
tiated ART between baseline and month 6 (who were included at month 6 and month 12) and
participants who initiated ART between month 6 and month 12 (who were included at month
12 only). The measure of association is the (adjusted) odds ratio for missing at least one dose of
ART for participants with suicidality compared with those without suicidality.
(iv).The time to the first visit to a health facility was used as a measure of health-seeking
behavior and was analyzed using odds of occurrence [15]. The primary exposure, suicidality,
was lagged, that is, suicidality at baseline was used as the exposure variable for a visit to a health
facility at month 6, whereas suicidality at month 6 was used as the exposure variable for a visit
to a health facility at month 12. The analysis adjusted for study site, sex, age, visit (i.e., month 6
or month 12), and baseline CD4 cell count as explanatory variables. Participants who had their
first visit to a health facility at baseline were excluded from the analysis, whereas those who vis-
ited a health facility between month 6 and month 12 were included at month 6 but excluded at
month 12. The measure of association is the (adjusted) odds ratio for a visit to a health facility
for participants with suicidality (at the previous visit) compared with those without suicidality.
v) Having engaged in risky sexual behavior (as measured by at least one affirmative answer
to the 5 questions on sexual behavior) was analyzed using discrete time survival models. The
primary exposure (suicidality) was lagged. The analysis adjusted for study site, sex, age, visit,
and baseline CD4 count as explanatory variables. Participants who had engaged in risky sexual
behavior at baseline were excluded from the analysis, whereas those who engaged in risky sex-
ual behavior at month 6 were excluded at month 12. The measure of association is the
(adjusted) odds ratio for risky sexual behavior for participants with suicidality (at the previous
visit) compared with those without suicidality. We did not adjust for multiple significance test-
ing. Although this increases the chance of type I errors, the aim of the analysis was to identify
potentially detrimental consequences of suicidality; this can be seen as analogous to safety
analysis in drug trials in which the aim is to identify potential risks caused by the investiga-
tional drug, in which case adjusting for multiplicity is not recommended [16,17].
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Ethics approval and consent to participate
The study obtained ethical approval from the Uganda Virus Research Institute’s Science and
Ethics Committee and the Uganda National Council of Science and Technology. Study partici-
pants were invited to consent and participate in this study by trained psychiatric nurses / psy-
chiatric clinical officer(s) after being provided with adequate information about the study.
Respondents found to have significant psychiatric problems were referred to psychiatric
departments nearest to their study sites for further assessment and management.
Results
At month 12 of follow up, the overall retention in the study was high 94.7% of the 1099 partici-
pants assessed at baseline. About 6% (n = 67) were lost to follow-up, of whom 1.6% (n = 18)
were confirmed to have died during the course of this study. The CD4 cell count increased sig-
nificantly with time, the amount of risky sexual activity reduced, number of health facility vis-
its decreased and the rate of suicidality also significantly reduced at both 6 months and 12
months of follow up (Table 1). Majority of the participants were female and the participant
mean age was 35 years. Most of them (73%) had primary or no formal education. A detailed
description of the characteristics of this study population can be found in an earlier publication
[6]. The number of participants at the two study sites was similar throughout the three report-
ing periods (baseline, 6 months and 12 months).
The proportion of participants with suicidality decreased from 2.9% (n = 32) at baseline to
roughly 1% both at month 6 (n = 9, 0.9%) and month 12 (n = 12, 1.2%). The CD4 count increased
over time–this increase was largely artefactual since those who started ART were excluded from
subsequent analysis of CD4 count. Few participants experienced a new WHO stage 3 or 4 event,
6% (n = 66) at baseline, 3.4% (n = 23) at month 6 and 4.6% (n = 25) at month 12 (Table 2).
Associations between psychosocial factors and HIV clinical and
behavioural outcomes
The results of fitting models for the associations between psychosocial exposures and HIV
related clinical and behavioural outcomes are shown in Tables 3and 4.Table 3 summarizes
the fitting of the multiple linear regression models to the log (CD4) counts at months 6 and 12.
None of the associations between suicidality and log (CD4) count approached statistical signif-
icance. Of the investigated clinical and behavioural outcomes, suicidality only had a negative
impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI
2.45–27.71, p>0.01) times higher for participants with suicidality compared to those without
suicidality. The following outcomes were not significantly impacted by baseline suicidality:
HIV clinical stage, CD4 count and risky sexual behaviour.
Table 4 summarizes the results of fitting logistic regression models for having missed a dose
of ART in the three days before the visit. The odds of missing a dose of ART were 8.25 (95%CI
2.45–27.71, p>0.01) times higher for participants with suicidality compared to those without
suicidality.
Table 5 summarizes the results of fitting discrete-time survival models for the outcomes of
time to first new WHO stage 3/4 event, time to visit a health facility, and time to risky sexual
behaviour.
Following the findings by Ironson et al [18] in their study on psychosocial factors that pre-
dicted CD4 and viral load change, the results can be quantified by looking at the Odds ratios
(OR) for an individual at the 75th percentile (P75) compared to a similar individual at the 25th
percentile (P25) of the scale.
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Table 1. Socio-demographics, suicidality and HIV related outcomes of the study population by data collection time period.
Factor Level Baseline Month 6 Month 12
Overall 1099 1059 1041
Socio-demographics
Study Site Entebbe 542 (49.3%) 520 (49.1%) 509 (48.9%)
Masaka 557 (50.7%) 539 (50.9%) 532 (51.1%)
Sex Male 252 (22.9%) 243 (23.0%) 238 (22.9%)
Female 847 (77.1%) 816 (77.0%) 803 (77.1%)
Age Mean (s.d.) 35.1 (9.3) 35.1 (9.3) 35.1 (9.1)
Median (IQR) 34 (28–41) 34 (28–41) 34 (28–41)
Age (grouped) 18–29 339 (30.8%) 321 (30.3%) 316 (30.4%)
30–34 252 (22.9%) 248 (23.4%) 244 (23.4%)
35–39 197 (17.9%) 188 (17.8%) 185 (17.8%)
40–49 225 (20.5%) 218 (20.6%) 216 (20.8%)
>= 50 86 (7.8%) 84 (7.9%) 80 (7.7%)
Education Status None 120 (10.9%) 113 (10.7%) 113 (10.8%)
Primary 680 (61.9%) 654 (61.8%) 641 (61.6%)
Secondary or more 296 (26.9%) 289 (27.3%) 284 (27.3%)
Missing 3 (0.3%) 3 (0.3%) 3 (0.3%)
Marital Status Currently married 563 (51.2%) 540 (51.0%) 533 (51.2%)
Widowed 163 (14.8%) 157 (14.8%) 158 (15.2%)
Separated / divorced 267 (24.3%) 261 (24.6%) 254 (24.4%)
Single 104 (9.5%) 99 (9.4%) 94 (9.0%)
Missing 2 (0.2%) 2 (0.2%) 2 (0.2%)
Religion Catholic 586 (53.3%) 566 (53.4%) 562 (54.0%)
Protestant 237 (21.6%) 228 (21.5%) 224 (21.5%)
Muslim 163 (14.8%) 158 (14.9%) 152 (14.6%)
Seventh Day 16 (1.5%) 16 (1.5%) 14 (1.3%)
Born Again 93 (8.5%) 87 (8.2%) 85 (8.2%)
Other 4 (0.4%) 4 (0.4%) 4 (0.4%)
Occupation Farmer / Fishing 324 (29.5%) 321 (30.3%) 310 (29.8%)
Professional / clerical 43 (3.9%) 42 (4.0%) 42 (4.0%)
Trader / Artisan / transport 396 (36.0%) 386 (36.4%) 383 (36.8%)
Unemployed / Retired / housewife 139 (12.6%) 126 (11.9%) 126 (12.1%)
Student / other 187 (17.0%) 174 (16.4%) 172 (16.5%)
Missing 10 (0.9%) 10 (0.9%) 8 (0.8%)
SES index Mean (s.d.) 15.1 (3.6) 15.1 (3.6) 15.1 (3.6)
Median (IQR) 15 (13–17) 15 (13–17) 15 (13–17)
CD4 count Mean (s.d.) 516.2 (267.6) 560.6 (235.4) 600.6 (233.4)
Median (IQR) 471 (352; 665) 517 (407; 687) 556 (435; 711)
Geometric mean (95% C.I.) 430.7 (412; 450) 514.6 (498; 532) 516.1 (497; 537)
WHO stage I 533 (48.5%) 308 (45.4%) 233 (43.3%)
II 500 (45.5%) 347 (51.2%) 265 (49.3%)
III / IV 66 (6.0%) 23 (3.4%) 25 (4.6%)
Missing 0 0 15 (2.8%)
Missed a dose of ART in past three days No 289 (86.8%) 390 (83.3%)
Yes 30 (9.0%) 31 (6.6%)
N/A 14 (4.2%) 47 (10.0%)
(Continued )
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On time to the first new WHO stage 3 or 4 event, the significant exposure was negative cop-
ing style. Increasing risk for a new WHO stage 3 or 4 event was associated with increasing neg-
ative coping style scores (OR 1.61). On the results of fitting discrete-time survival models for
the time to the first visit to a health facility, the significant psychosocial factors were social sup-
port, negative life events, and suicidality. The risk of visiting a health facility increased with:
decreasing social support scores (nonlinear effect, OR for P25 vs. P75 was 1.12) and increasing
negative life events scores (OR for P75 vs. P25 was 1.31).
Table 1. (Continued)
Factor Level Baseline Month 6 Month 12
Visits to health facility in past month None 781 (71.1%) 603 (80.1%) 507 (86.7%)
Once 146 (13.3%) 70 (9.3%) 47 (8.0%)
Twice 85 (7.7%) 45 (6.0%) 18 (3.1%)
Three or more 86 (7.8%) 31 (4.1%) 10 (1.7%)
Missing 1 (0.1%) 4 (0.5%) 3 (0.5%)
Any Risky sexual activity No 950 (86.4%) 832 (91.0%) 737 (90.9%)
Yes 149 (13.6%) 74 (8.1%) 66 (8.1%)
Missing 0 8 (0.9%) 8 (1.0%)
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Table 2. Suicidality and HIV related outcomes of the study population by data collection time period.
Factor Level Baseline Month 6 Month 12
Overall 1099 1059 1041
Psychosocial exposures
Suicidality No 1067 (97.1%) 1041 (98.3%) 1020 (98.0%)
Yes 32 (2.9%) 9 (0.9%) 12 (1.2%)
Missing 0 9 (0.9%) 9 (0.9%)
HIV related outcomes
CD4 count Mean (s.d.) 516.2 (267.6) 560.6 (235.4) 600.6 (233.4)
Median (IQR) 471 (352; 665) 517 (407; 687) 556 (435; 711)
Geometric mean 430.7 514.6 516.1
WHO stage I 533 (48.5%) 308 (45.4%) 233 (43.3%)
II 500 (45.5%) 347 (51.2%) 265 (49.3%)
III / IV 66 (6.0%) 23 (3.4%) 25 (4.6%)
Missing 0 0 15 (2.8%)
Patients who initiated ART
Missed a dose of ART in past three days No 289 (86.8%) 390 (83.3%)
Yes 30 (9.0%) 31 (6.6%)
N/A 14 (4.2%) 47 (10.0%)
Visits to health facility in past month None 781 (71.1%) 603 (80.1%) 507 (86.7%)
Once 146 (13.3%) 70 (9.3%) 47 (8.0%)
Twice 85 (7.7%) 45 (6.0%) 18 (3.1%)
Three or more 86 (7.8%) 31 (4.1%) 10 (1.7%)
Missing 1 (0.1%) 4 (0.5%) 3 (0.5%)
Any Risky sexual activity No 950 (86.4%) 832 (91.0%) 737 (90.9%)
Yes 149 (13.6%) 74 (8.1%) 66 (8.1%)
Missing 0 8 (0.9%) 8 (1.0%)
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The psychosocial factors that significantly impacted missing a dose of ART were social sup-
port, negative life events and suicidality. The odds of missing a dose of ART were higher for
participants with: lower social support scores (OR for P25 vs. P75 was 1.21; the non-linear
effect could be noted that this is similar to the OR for P10 vs. P25 which was 1.20 despite cover-
ing a much narrower range of participants) and higher negative life events scores (OR for P75
vs. P25 was 1.57).
Discussion
This cohort study aimed to determine the effect of suicidality on clinical and behavioural out-
comes among adults living with HIV/AIDS in Uganda. We found a positive association
between suicidality and poor clinical and behavioural outcomes. Compared to previous stud-
ies, we looked at a broader range of psychosocial exposures and indices of HIV related out-
comes. In this paper we discuss the effect of suicidality and psychosocial exposures on indices
of HIV related outcomes with the latter grouped under the domains of HIV disease progres-
sion, drug adherence, health seeking behaviour and risky sexual behaviour.
In this study, suicidality predicted risky sexual behaviour. According to our knowledge, this
is the first study that has investigated the impact of suicidality on clinical and behavioural out-
comes among individuals with HIV in low resource settings. Previous studies have investigated
the longitudinal impact of depression on HIV outcomes. For example, a study of depression
Table 3. Regression models for log (CD4) counts (effects expressed as geometric mean ratios).
Factor Level Effect as GMR (95% CI)�P-value
Study Site Entebbe 1 (baseline) <0.00
Masaka 1.11 (1.06; 1.16)
Sex Male 1 (baseline) 0.02
Female 1.07 (1.01; 1.14)
Age Per 10 year increase 0.99 (0.96; 1.01) 0.33
Month Per 6 month increase 1.06 (1.02; 1.09) 0.00
Baseline CD4 count Per 1 log
10
increase 2.63 (1.95; 3.54) 0.01
Suicidality No 1 (baseline) 0.16
Yes 1.12 (0.96; 1.32)
Note �Effects shown in this column are adjusted for socio-demographic factors and baseline CD 4 counts.
https://doi.org/10.1371/journal.pone.0254830.t003
Table 4. Logistic regression models for missed ART doses with robust estimation of variance.
Factor Level Odds Ratio (95% CI)�P-value
Study Site Entebbe 1 (baseline) 0.02
Masaka 0.46 (0.25; 0.88)
Sex Male 1 (baseline) 0.43
Female 0.75 (0.45; 1.26)
Age Per 10 year increase 0.97 (0.72; 1.31) 0.86
Month Per 6 month increase 0.75 (0.45; 1.26) 0.28
Suicidality No 1 (baseline) 0.00
Yes 8.25 (2.45; 27.71)
Note 1 The social support variable used here is 2500/ (Social Support).
�Effects shown in this column are adjusted for socio-demographic factors and baseline CD4 counts.
�NB: IQR-Interquartile range, GMR- Geometric Mean Ratio, SD-standard deviation.
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by Kinyanda et al (2018) reported a negative association between depression and ART adher-
ence and health seeking behaviour [6]. A study by Bhatia and colleagues in the united states of
America also reported a negative relationship between depression and health seeking behav-
iour [19].
Two indices were used to assess HIV disease progression in this study, namely, CD4 count
and time to the first new WHO stage 3 or 4 event. Only negative coping style was a significant
predictor of time to the first WHO stage 3 or 4 event with none of the investigated exposures
predicting trends in CD4 counts. Studies undertaken elsewhere have previously reported nega-
tive coping style as a predictor of faster HIV disease progression [20–22]. The relationship
between psychosocial exposures and CD4 counts could have been confounded by extraneous
factors given that CD4 counts in this study showed wide variability both between subjects and
between time periods within subjects.
Health seeking behaviour in this study was assessed using time to first visit to a health facil-
ity. The psychosocial exposures which predicted increased utilisation of health facilities were
poor social support, increasing number of negative life events and suicidality. The increased
utilisation of HIV care services that was associated with the psychosocial exposures of poor
social support, increasing negative life events and suicidality observed in this study may have
been a ‘cry for help’ from persons experiencing psychosocial distress whose needs were not
being met by an HIV care system that is not yet responsive to mental health and other psycho-
social problems.
A limitation of this study is that some of the indices used to assess HIV related outcomes
may have been confounded by factors outside the study. We attempted to control for this for
one of the outcomes domain by having two indices to represent it. This however had to be
weighed against the danger of having too many comparisons which would increase the risk of
Table 5. Discrete time survival models for various clinical and behavioural outcomes.
Factor Level Odds Ratio (95% CI)�P-value
New WHO stage 3 / 4 event
Negative coping style scores Per 1 s.d. increase 1.40 (1.05; 1.88) 0.02
Social support scores Per 1 s.d. increase 0.97 (0.72; 1.31) 0.83
Negative life events scores Per 1 s.d. increase 0.80 (0.57; 1.10) 0.17
Suicidality No 1 (baseline) 0.73
Yes 1.44 (0.18; 11.29)
Time to visit a health facility
Negative coping style scores Per 1 s.d. increase 0.89 (0.77; 1.03) 0.12
Social support scores
2
Per 1 s.d. increase 1.16 (1.06; 1.27) 0.00
Negative life events scores Per 1 unit increase 1.26 (1.09; 1.46) 0.00
Suicidality No 1 (baseline) 0.07
Yes 2.49 (0.93; 6.67)
Time to risky sexual behaviour
Negative coping style scores Per 1 s.d. increase 1.12 (0.94; 1.33) 0.22
Social support scores Per 1 s.d. increase 1.08 (0.89; 1.30) 0.44
Negative life events scores Per 1 unit increase 0.99 (0.84; 1.19) 0.97
Suicidality No 1 (baseline) 0.39
Yes 0.42 (0.056; 3.13)
Note: The social support variable used here is 2500/ (Social Support)
�Effects shown in this column are adjusted for socio-demographic factors and baseline CD4 counts only.
IQR-Interquartile range, GMR- Geometric Mean Ratio, SD-standard deviation.
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producing spurious results purely by chance. Therefore, to assess for the outcomes domain of
HIV disease progression in this study, we used the indices of both CD4 cell counts (which
showed extreme variability in this study) and the variable ‘new WHO stage 3 or 4 event’
(which showed more stability).
The investigated psychosocial exposures impacted all the investigated HIV related out-
comes domains with suicidality impacting the most domains (three out of the four investigated
HIV outcomes domains). These results suggest that to improve HIV related outcomes among
patients accessing HIV care, there is a need to screen for and triage patients with significant
mental health and psychosocial problems so that they can receive treatment for the mental
health problems and additional psychosocial support to help them navigate through HIV care.
Secondly, in order to optimise effectiveness of interventions aimed at improving HIV related
outcomes, there may be a need to include components that address suicidality and other
important psychosocial exposures such as the cognitive behavioural therapy for adherence and
depression (CBT-AD) which has been shown to significantly improve depression and ART
adherence outcomes [23]. However, since we know very little regarding the biological mecha-
nisms underlying the observed relationships between exposures and outcomes [24] and that
between suicidality and the other psychosocial exposures themselves, there is need for research
in this area.
Conclusions
The fact that baseline suicidality significantly and negatively impacted ART adherence calls for
the incorporation of psychosocial interventions to target indices of psychological distress such
as suicidality to improve HIV related clinical and behavioural outcomes.
Supporting information
S1 Checklist.
(PDF)
S1 Data.
(DTA)
Acknowledgments
The authors wish to thank the participants for their time and trust. They also thank the manag-
ers of the two HIV clinics and the leadership of The AIDS Support Organisation (TASO) in
Uganda for permitting the study to be conducted at their specialised clinics. Special gratitude
is extended to the staff working at the specialised HIV/AIDS clinics where the study was con-
ducted. Appreciation is extended to the diligent work of research assistants.
Author Contributions
Conceptualization: Godfrey Zari Rukundo, Richard Stephen Mpango, Vikram Patel, Eugene
Kinyanda.
Formal analysis: Jonathan Levin.
Funding acquisition: Eugene Kinyanda.
Methodology: Jonathan Levin, Eugene Kinyanda.
Supervision: Richard Stephen Mpango, Eugene Kinyanda.
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Writing – original draft: Godfrey Zari Rukundo.
Writing – review & editing: Godfrey Zari Rukundo, Jonathan Levin, Richard Stephen
Mpango, Vikram Patel, Eugene Kinyanda.
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ResearchGate has not been able to resolve any citations for this publication.
Background:
There is still wide variability in HIV disease course and other HIV related outcomes, attributable in part to psychosocial factors such as major depressive disorder (MDD), a subject that has received little attention in sub-Saharan Africa.
Methods:
Using a longitudinal cohort of 1099 HIV positive antiretroviral therapy (ART) naïve persons, we investigated the impact of MDD on four HIV related negative outcome domains in Uganda. MDD was assessed using a Diagnostic Statistical Manual IV based tool. Also collected was data on surrogate measures of the HIV related outcome domains. Data was collected at the three time points of baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to investigate the relationship between MDD and indices of the HIV outcomes.
Results:
MDD was a significant predictor of 'missed ART doses' (aOR=4.75, 95% CI, 1.87-12.04, p=0.001), 'time to first visit to healthy facility' (aOR=1.71; 95% CI, 1.07-2.73; p=0.024), 'time to first self-reported risky sexual activity' (aOR=2.11, 95% CI, 1.27-3.49; p=0.004) but not of 'CD4 counts at months 6 and 12' (estimated effect 29.0; 95% CI, -7.8-65.7; p=0.12) and 'time to new WHO stage 3 or 4 clinical event' (aOR=0.52, 95% CI, 0.12-2.20, p=0.37).
Conclusion:
MDD significantly impacted three of the four investigated outcome domains. These results by demonstrating the adverse consequences of an untreated mental health disorder (MDD) on HIV related outcomes, further strengthen the need to urgently act on WHO's call to integrate mental health care in general HIV care.
Background
Suicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care.
Methods
The ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors.
Results
Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk.
Conclusions
Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV.
Suicidal behavior is a leading cause of death and disability worldwide. Fortunately, recent developments in suicide theory and research promise to meaningfully advance knowledge and prevention. One key development is the ideation-to-action framework, which stipulates that (a) the development of suicidal ideation and (b) the progression from ideation to suicide attempts are distinct phenomena with distinct explanations and predictors. A second key development is a growing body of research distinguishing factors that predict ideation from those that predict suicide attempts. For example, it is becoming clear that depression, hopelessness, most mental disorders, and even impulsivity predict ideation, but these factors struggle to distinguish those who have attempted suicide from those who have only considered suicide. Means restriction is also emerging as a highly effective way to block progression from ideation to attempt. A third key development is the proliferation of theories of suicide that are positioned within the ideation-toaction framework. These include the interpersonal theory, the integrated motivational-volitional model, and the three-step theory. These perspectives can and should inform the next generation of suicide research and prevention. Expected final online publication date for the Annual Review of Clinical Psychology Volume 12 is March 28, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Globally, suicide and HIV/AIDS remain two of the greatest healthcare issues, particularly in low- and middle-income countries. Several studies have observed a relationship between suicidal behaviour and HIV/AIDS.
Materials and Methods
. The main objective of this research was to determine the prevalence of elevated risk of suicidal ideation in HIV-positive persons immediately following voluntary HIV counselling and testing (VCT). The study sample consisted of adult volunteers attending the VCT clinic at a university-affiliated, general state hospital. Participants completed a sociodemographic questionnaire, Beck’s Hopeless Scale, and Beck’s Depression Inventory.
Results
. A significantly elevated risk of suicidal ideation was found in 83.1% of the patients who tested seropositive. Despite a wide age range in the cohort studied, the majority of patients with suicidal ideation were males in the younger age group (age < 30 years), consistent with the age-related spread of the disease and an increase in suicidal behaviour in younger people. Relevant associated variables are discussed.
Conclusion
. The results serve as important markers that could alert healthcare professionals to underlying suicide risks in HIV-positive patients. It is recommended that screening for elevated risk of suicidal ideation and prevention of suicidal behaviour should form a routine aspect of comprehensive patient care at VCT clinics.
Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.
Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretrovial therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.
Background:
Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD.
Methods:
In this three-arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat.
Findings:
Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1·00 percentage point per visit, 95% CI 0·34 to 1·66, p=0·003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference -0·41, -0·66 to -0·16, p=0·001; Montgomery-Asberg depression rating scale [MADRS] score -4·69, -8·09 to -1·28, p=0·007; clinical global impression [CGI] score -0·66, -1·11 to -0·21, p=0·005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported.
Interpretation:
Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches.
Funding:
National Institute of Mental Health, National Institute of Allergy and Infectious Diseases.
In this article, we show how discrete-time survival analysis can address questions about onset, cessation, relapse, and recovery. Using data on the onset of suicide ideation and depression and relapse into cocaine use, we introduce key concepts underpinning the method, describe the action of the discrete-time hazard model, and discuss several types of main effects and interactions that can be included as predictors. We also comment on practical issues of data analysis and strategies for interpretation and presentation.
Background:
Suicide rates have been reported at elevated levels among people living with HIV/AIDS. We sought to characterize longitudinal suicide rates among people living with HIV/AIDS who are accessing free highly active antiretroviral treatment (HAART) in British Columbia and evaluate the sociodemographic, clinical and behavioural factors associated with suicide in this population.
Methods:
Retrospective analysis of all patients in the HAART Observational Medical Evaluation and Research (HOMER) cohort who were 19 years of age and older who started treatment between August 1996 and June 2012. The primary outcome variable was death due to suicide. Data on deaths were obtained monthly through a linkage with the British Columbia Ministry of Health Vital Statistics Agency. Logistic regression and Cox proportional hazards models were used to identify factors independently associated with suicide mortality.
Results:
A total of 993 deaths among 5229 patients accessing treatment were recorded, of which 82 (8.2%) were caused by suicide. Death from suicide peaked at 961 deaths per 100 000 person-years in 1998 and declined to 2.81 deaths per 100 000 person-years in 2010. Cox regression analysis showed that a history of injection drug use (adjusted hazard ratio [AHR] = 3.95, 95% confidence interval [CI] 1.99-7.86) or having no experience with an AIDS-defining illness (AHR = 4.45, 95% CI 1.62-12.25) were factors independently associated with suicide. This model showed a 51% reduction (AHR = 0.49, 95% CI 0.45-0.54) in the suicide rate per calendar year.
Interpretation:
Deaths from suicide declined substantially over time, and factors other than progression of HIV disease, such as injection drug use, may be important targets for intervention to reduce suicide risk.