Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa
Africa. PLoS ONE 8(1): e55305. doi:10.1371/journal.pone.0055305
Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa
Paul K. Drain 0
Elena Losina 0
Gary Parker 0
Janet Giddy 0
Douglas Ross 0
Jeffrey N. Katz 0
Sharon M. Coleman 0
Laura M. Bogart 0
Kenneth A. Freedberg 0
Rochelle P. Walensky 0
Ingrid V. Bassett 0
Julian W. Tang, Alberta Provincial Laboratory for Public Health/ University of Alberta, Canada
0 1 Division of Infectious Diseases, Massachusetts General Hospital , Boston , Massachusetts, United States of America, 2 Division of General Medicine, Massachusetts General Hospital , Boston , Massachusetts, United States of America, 3 Medical Practice Evaluation Center, Massachusetts General Hospital , Boston , Massachusetts, United States of America, 4 Department of Medicine, Brigham and Women's Hospital , Boston , Massachusetts, United States of America, 5 Department of Orthopedic Surgery, Brigham and Women's Hospital , Boston , Massachusetts, United States of America, 6 Division of Rheumatology, Brigham and Women's Hospital , Boston , Massachusetts, United States of America, 7 Center for AIDS Research, Harvard Medical School , Boston , Massachusetts, United States of America, 8 Department of Pediatrics, Harvard Medical School , Boston , Massachusetts, United States of America, 9 Departments of Epidemiology and Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, United States of America, 10 Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America, 11 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America, 12 Data Coordinating Center, Boston University School of Public Health, Boston, Massachusetts, United States of America, 13 Boston Children's Hospital , Boston , Massachusetts, United States of America, 14 Department of Medicine, McCord Hospital , Durban , South Africa , 15 Department of Medicine, St. Mary's Hospital , Durban , South Africa
Background: After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. Methods: We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. 3 All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count ,100 cells/mm . We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing (''competing needs to healthcare'') on presentation with late-stage HIV disease. Results: Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived $5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4), were male (AOR 1.7, 95% CI 1.2-2.3), worked outside the home (AOR 1.5, 95% CI 1.1-2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9) had higher odds of late-stage HIV disease presentation. Conclusions: Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.
Funding: This research was supported by the Harvard Institute for Global Health (PKD); the Fogarty International Clinical Research Scholars and Fellows Program
at Vanderbilt University R24 TW007988 (PKD); the National Institute of Mental Health R01 MH090326 (IVB) and R01 MH073445 (RPW); the National Institute of
Allergy and Infectious Disease K24 AI062476 (KAF); the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Arthritis and
Musculoskeletal and Skin Diseases K24 AR057827 (EL); the National Center for Research Resources (the Harvard Catalyst UL1 RR 025758); the Burke Global Health
Fellowship (IVB); and the Claflin Distinguished Scholar Award (IVB). The funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
South Africa has more HIV-infected people than any other
country, and over 1.4 million South Africans are now receiving
antiretroviral therapy (ART) [1,2]. However, despite this progress,
4551% of ART-eligible people are still not receiving treatment
[1,3]. Not only do these HIV-infected people constitute nearly
one-quarter of all AIDS-related deaths in sub-Saharan Africa, but
they also transmit HIV to others . Furthermore, late-stage HIV
disease at initial HIV diagnosis has been associated with poor
treatment response rates and higher mortality . In August
2011, the South African Department of Health increased the ART
initiation threshold from CD4,200 to ,350 cells/mm3 to help
reduce AIDS-related deaths . However, the median CD4
Age $40 years 249 (30.0)
Age ,40 years 581 (70.0)
Male 415 (50.0)
Female 415 (50.0)
Did not complete high school 449 (54.1)
Did complete high school 381 (45.9)
Never married 666 (80.2)
Currently married 123 (14.8)
Divorced/separated 13 (1.6)
Widowed 28 (3.4)
If not married, in current relationship?
No 226 (32.0)
Yes, ,6 months 84 (11.9)
Yes, $6 months 397 (56.2)
Currently working outside home 469 (56.5)
Not currently working outside home 361 (43.5)
Working ,20 hours outside home 32 (6.8)
Working $20 hours outside home 437 (93.2)
Proximity to the HIV Clinic
Distance to clinic $5 kilometers 688 (82.9)
Distance to clinic ,5 kilometers 142 (17.1)
Travel time to clinic $30 minutes 303 (36.5)
Travel time to clinic ,30 minutes 527 (63.5)
Health Care Usage
No prior HIV testing 661 (79.7)
Any prior HIV testing 168 (20.3)
Any overnight hospital stay in last year 60 (7.2)
No overnight hospital stay in last year 770 (92.8)
Emotional Health and Social Support
Poor Emotional Health (, median value) 399 (48.1)
Good Emotional Health ($ median value) 431 (51.9)
Poor Social Support (, median value) 416 (50.1)
Good Social Support ($ median value) 414 (49.9)
Competing Needs to Healthcare
Gone without healthcare because needed 227 (27.3)
money for food, clothing, or housing
Never gone without healthcare because needed 603 (72.6)
money for food, clothing, or housing
Foregone food, clothing, or housing because 196 (23.6)
needed money for healthcare
Never foregone food, clothing, or housing 634 (76.4)
because needed money for healthcare
McCord Hospital 437 (52.7)
St. Marys Hospital
count at the time of ART initiation was 111 cells/mm3 in a recent
large South African cohort .
Increasing the CD4 count treatment threshold will have little
benefit if the majority of people continue to present with
dangerously low CD4 counts and late-stage HIV disease.
Strategies to reduce AIDS-related mortality and decrease HIV
transmission must include earlier diagnosis of HIV , which has
been shown to improve survival . Intensified efforts to promote
early diagnosis of HIV-infected people in resource-limited settings
are needed, but little is known about how to best target people in
HIV testing campaigns [15,16]. We conducted a large, prospective
study to assess both the real and perceived barriers to presenting
for HIV care in South Africa.
Sites and participants
We studied adults who presented for voluntary HIV counseling
and testing at four outpatient clinical sites in Durban from August
2010 to November 2011. McCord Hospital is an urban,
stateaided general hospital that serves the greater Durban area. St.
Marys Hospital in Mariannhill is a state-aided general hospital
that serves a resource-limited population in a peri-urban area of
Durban. Both McCord Hospital and St. Marys Hospital have
high-volume outpatient HIV clinics that have been providing
ART since 2001 and 2003, respectively, and receiving Presidents
Emergency Plan for AIDS Relief (PEPFAR) support since 2004.
The other two sites, Tshelimnyama and Marianridge, are
municipal primary health clinics located within the catchment
Have to wait too long to see the nurse/doctor 261 (31.4)
Could not afford medications
Could not afford the cost of transportation
Could not arrange transport to the clinic
Could not get time off work
Did not know where to find care
Had to take care of someone else
The nurse/doctor does not speak my language 71 (8.6)
Were not treated with respect by
area of St. Marys Hospital. Throughout the course of the study,
all four outpatient sites offered free HIV counseling and testing
during normal working business hours.
We offered enrollment to all adults $18 years of age prior to
HIV counseling and testing. We excluded those already known to
be HIV-infected, pregnant, or unwilling to share their HIV test
result with the research team. HIV testing, as well as participation
in the study, carried no financial costs to the participant. All
participants provided written informed consent either in English or
Zulu. The study was approved by the ethics committees of
McCord Hospital and St. Marys Hospital in Durban, and
Partners HealthCare (Protocol #: 2006-P-001379) in Boston.
We asked participants about personal demographics, proximity
to the HIV clinic, and prior healthcare usage and HIV testing. We
recorded responses to 12 questions related to perceived personal
barriers for seeking HIV testing and medical care during the prior
6 months . We asked 5 questions about emotional health over
the previous month with each response rated on a 6-point Likert
scale (ranging from 1 being all of the time or always to 6
being none of the time or never). These questions, which
were adapted from the 5-item Mental Health Inventory (MHI-5)
screening test, were used to calculate a mental health composite
(MHC) score . We asked 13 questions about availability of
personal social support with each response rated on a 5-point
Likert scale (ranging from 1 being none of the time to 5 being
all of the time). These questions incorporate four social support
scales (emotional/informational, tangible, positive interaction,
affectionate), and were used to calculate the Social Support Index
(SSI), from the Medical Outcomes Study . Both the MHC and
SSI scores were independently averaged and then transformed to
scores ranging from 1 to 100, with higher numbers signifying
better emotional health and more social support. We asked
participants if they had gone without food, clothing, or housing
(basic necessities) during the prior 6 months because they
needed money for healthcare, or if they had foregone healthcare
during the prior 6 months because they needed money for food,
clothing, or housing .
After completing the survey, participants were offered free HIV
counseling and testing, and HIV-infected participants were offered
free CD4 count testing. Those who tested positive for HIV were
referred for appropriate care and treatment. All HIV testing, care,
and treatment was provided in accordance with current South
African Department of Health HIV testing and treatment
Late-stage HIV disease presentation was defined as a CD4
count ,100 cells/mm3 at the time of initial HIV diagnosis. To
allow incorporation of the perceived barriers into multivariate
models, while also minimizing possible collinearity, we categorized
the 12 barriers into 5 groups (service delivery, financial, personal
health perception, logistical, and structural). Service delivery
barriers included have to wait too long to see the nurse/doctor,
the nurse/doctor does not speak my language, and not treated
with respect by the nurse/doctor. Financial barriers included
could not afford medications and could not afford the cost of
transportation. Personal health perception barriers included
didnt think it was necessary, because didnt feel sick and felt
too sick. Logistical barriers included could not get time off
work and had to take care of someone else. Structural barriers
included could not get to the clinic during the hours it was open,
could not arrange transport to the clinic, and did not know
where to find care. Poor emotional health and poor social
support were defined as an MHC and SSI score below the median
We used Chi-squared and Fishers Exact tests to compare
potential risk factors between those presenting with and without
late-stage HIV disease. We used an iterative model building
approach to construct a series of logistic regression models to
identify factors associated with late-stage disease presentation.
First, we used bivariate logistic regression models to determine
odds ratios (OR) of presenting with late-stage HIV disease. To
Ratio (95% CI)
Odds Ratio (95% CI)
N Living .5 kilometers from the test site
N Reported competing needs to healthcare
N Worked outside the home
N Perceived health service delivery barrier
N Poor emotional health
build a multivariate logistic regression model and generate
adjusted odds ratios (AOR), we included age, sex, and any
variable with a p-value ,0.15 in bivariate analyses into a single
model. We then removed one variable at a time for those variables
with a p-value .0.15, and after each variable was removed, the
model was refit to evaluate the remaining variables. Finally,
variables not selected based on the initial unadjusted analyses were
included in the multivariate model to assess their significance in
the presence of other variables, and all variables were retained if
they had p-values ,0.15. To minimize the potential for
collinearity, we assessed the correlation between all pairs of
independent variables and verified that no pair of variables
included in the same regression model was highly correlated with a
Spearman r .0.60. All reported p-values were two-tailed, and a
pvalue ,0.05 was considered statistically significant. We conducted
analyses using SAS software (version 9.2; SAS Institute, Cary,
Among 3,669 people screened for the study, 2,694 met
eligibility criteria and enrolled in the study. Among those enrolled,
1,026 (38.1%) tested positive for HIV, of which 830 adults (80.9%
of HIV-infected participants) completed both CD4 testing and the
study survey. Among those, the median CD4 count was 186 cells/
mm3 (interquartile range 70345 cells/mm3), and 279 (33.6%)
participants had late-stage HIV disease at the time of their initial
Within the cohort, 249 (30.0%) were .40 years of age, 415
(50.0%) were male, and 449 (54.1%) had not completed high
school (Table 1). Over half (56.5%) worked outside the home,
and 688 (82.9%) participants reported living $5 kilometers from
the clinic. Most participants (79.7%) had never previously been
tested for HIV, including 54 of the 60 participants (90.0%) who
had spent an overnight in a hospital during the prior year.
Reported HIV testing of participants hospitalized during the
prior year (6/60 or 10.0%) was significantly lower than the
reported HIV testing among participants who had not been
hospitalized during the prior year (162/769 or 21.1%) (p = 0.04).
Competing needs to healthcare
Overall, 227 (27.3%) participants had ever gone without
healthcare because they needed money for basic necessities (food,
clothing, or housing). In bivariate analysis, this was more
common among those presenting with late-stage HIV disease
(p = 0.02). Participants who presented with late-stage disease were
also more likely to have gone without healthcare to pay for food
(23.3% vs. 16.3%, p = 0.02), housing (22.5% vs. 15.6%, p = 0.04),
N Provide mobile HIV testing services
N Provide financial assistance to those at risk
N Offer periodic HIV screening at employment and business locations
N Expand clinic HIV testing hours to include nights and weekends
N Provide travel vouchers to those presenting for HIV testing
N Increase depression screening in the community
N Strengthen integration of mental health services into primary health care
and food and housing (13.3% vs. 7.6%, p = 0.009) (Figure 1, top).
Similarly, 196 participants (23.6%) had ever foregone basic
necessities because they needed money for healthcare.
Participants who presented with late-stage disease were more likely to
have foregone housing (18.6% vs. 13.2%, p = 0.04), and food and
housing (10.8% vs. 6.4%, p = 0.03) to pay for healthcare
(Figure 1, bottom).
Perceived barriers to medical care
The most commonly reported perceived barriers to medical
care were have to wait too long to see the nurse or doctor
(31.4%), could not afford medications (26.0%), and didnt
think it was necessary, because didnt feel sick (24.7%) (Table 2).
Participants who reported a perceived barrier of felt too sick
had a 2.97-fold higher odds (95% CI 2.004.41) of late-stage
HIV disease presentation. Perceived barriers of could not afford
the cost of transportation (OR 1.80, 95% CI 1.292.29), could
not afford medications (OR 1.79, 95% CI 1.302.46), could
not arrange transport to the clinic (OR 1.71, 95% CI 1.20
2.43), have to wait too long to see the nurse/doctor (OR 1.49,
95% CI 1.102.02), and could not get to the clinic during the
hours it was open (OR 1.46, 95% CI 1.042.05) were also more
commonly reported among those presenting with late-stage HIV
Factors associated with late-stage HIV disease
In the multivariate logistic regression model (Table 3), factors
associated with presentation to care with late-stage HIV disease
were living $5 kilometers from the clinic, having gone without
healthcare because money was needed for basic necessities, being
male, working outside the home, having a perception of health
service delivery barriers, and poor emotional health. Living
$5 kilometers from the clinic conferred a 2.80-fold (95% CI
1.684.67) higher odds of presenting with late-stage HIV disease.
Having gone without healthcare because money was needed for
basic necessities (AOR 1.67, 95% CI 1.172.37), being male
(AOR 1.66, 95% CI 1.222.26), and working outside the home
(AOR 1.48, 95% CI 1.072.05) had higher odds of late-stage HIV
disease presentation. Among the categories of perceived barriers to
medical care, only a perception of barriers related to health service
delivery (AOR 1.48, 95% CI 1.072.05), which included have to
wait too long to see the nurse/doctor, was significantly associated
with late-stage HIV disease presentation in multivariate analyses.
Finally, while both poor emotional health and poor social support
were significant in bivariate analyses, only poor emotional health
(AOR 1.41, 95% CI 1.031.94) was significant in the multivariate
As both guidelines and data increasingly support earlier HIV
treatment, it is imperative to understand why patients continue to
present with advanced HIV. In a large cohort of outpatient clinic
attendees newly diagnosed with HIV in South Africa, the main
risk factors for presenting with late-stage HIV disease were living
further from the clinic, being male, and having gone without
healthcare to pay for basic living necessities. Other variables
associated with late-stage disease presentation were working
outside the home, having a perception of barriers to health
service delivery, such as long wait times, and having poor
emotional health. These findings provide focused targets for
improving HIV testing programs in order to diagnose people
earlier and reduce the number of adults presenting to care with
late-stage HIV disease.
Several studies have examined risk factors for late-stage disease
presentation in sub-Saharan Africa. In Uganda, studies by Kigozi
et al. and Wanyenze et al. found significant risk factors were being
male, older, and having no secondary education, similar to our
findings [21,22]. They additionally found that people receiving
healthcare in a non-medical setting (pharmacy, home, or by
traditional healer) or having many sexual partners, both of which
were variables we did not obtain, were more likely to present with
late-stage disease. In Ethiopia, which has a very different cultural
population than South Africa, non-pregnant women, frequent
alcohol users, those in a long-term relationship, and people who
perceived ART to have many side effects or HIV as a stigmatizing
disease were more likely to present with late-stage disease . In
our cohort, relationships longer than 6 months had no impact on
late-stage presentation, and we did not assess alcohol use or
perception of HIV as a stigmatizing disease. The current study is
unique from these previous studies by assessing distance to the
clinic, perceived barriers to healthcare, competing needs to
healthcare, and emotional health and social support structures,
before participants were aware of their HIV-infected status.
In our cohort, several structural barriers, such as longer distance
to the clinic, a perception of poor service delivery, and working
outside the home, were among the strongest risk factors for
latestage HIV disease. Other studies in Africa have shown similar
structural barriers, such as longer distances and higher
transportation costs, to be related to loss-to-care before ART initiation
. One potential approach to ensuring better service
delivery and earlier HIV diagnosis could be the use of active,
mobile HIV testing strategies .
Despite the frequent occurrence of late-stage HIV disease
presentation in sub-Saharan Africa, there has been an incomplete
and inconsistent understanding of the perceived personal barriers
to HIV testing . In Botswana, perceived barriers to HIV
testing included fear of learning ones status, lack of perceived HIV
risk, and fear of having to change sexual practices if positive .
In Ethiopia, a perception of HIV as a highly stigmatizing disease
was common among people who presented with late-stage disease
. Although we did not assess HIV-related stigma, our findings
indicate that a perception of service delivery, structural, or
financial barriers are obstacles that prevented people from
learning their HIV-infected status.
Over one-quarter of those in our cohort reported having gone
without healthcare because they needed money for basic
necessities, and they were more likely to present with late-stage
disease. In several sub-Saharan African studies, food insecurity has
been associated with poor ART adherence, more opportunistic
infections, missed clinic visits, and increased hospitalizations [34
36]. Food insecurity is more common among older, unmarried,
HIV-infected adults , and thus food insecurity should be
addressed as part of comprehensive HIV treatment programs in
resource-limited settings . While our findings support the
observed negative effects of food insecurity, our results suggest that
housing insecurity is also a common problem and associated with
late-stage HIV disease presentation.
We found that poor emotional health and social support, both
of which were assessed before HIV testing, were associated with a
higher likelihood of presentation with late-stage HIV. Depression
is common among HIV-infected adults [38,39], and mental health
problems are vastly undertreated in resource-poor settings [40,41].
Rates of depression are also higher in symptomatic HIV-infected
people . While little data exists on outcomes among
HIVinfected adults with mental health issues in developing countries,
one U.S.-based study found higher rates of mortality among
HIVinfected adults with depression . Studies from Uganda and
Ethiopia have reported conflicting results about whether poor
mental health influences ART adherence [44,45]. While evidence
has been lacking on the association between mental health
disorders and uptake of diagnostic and treatment services for HIV
, our findings suggest that mental health issues and poor social
support structures may be important risk factors for delayed HIV
In our study, which excluded known HIV-infected adults, the
60 participants who had been hospitalized during the prior year
represented important missed opportunities for HIV testing.
Surprisingly, self-reported prior HIV testing was less common
among those who had been hospitalized, since South African
guidelines recommend offering HIV testing to all clients
attending health-care facilities as a standard component of medical
care, unless the client actively refuses . Our finding suggests
that either providers were not adherent to national guidelines or
hospitalized patients refused HIV testing at very high rates (90%).
Regardless, those missed opportunities represented 7.2% of our
cohort, suggesting that HIV testing of hospitalized patients
Our findings were primarily limited by the accuracy of
selfreported survey data. In this cross-sectional survey, we were not
able to determine causality with associations and the analysis was
not designed to fully examine the social stigma of HIV as a barrier
to testing. We used a definition of late-stage HIV disease of
CD4,100 cells/mm3, which portends a major risk for
cryptococcal meningitis, a leading cause of AIDS-related deaths in
subSaharan Africa . This definition allowed us to identify risk
factors and perceived barriers among the people with the greatest
risk for severe opportunistic infections and mortality. While we did
not assess some variables shown to be associated with late-stage
presentation in other African studies (alcohol consumption,
number of sexual partners, or ownership of material goods), we
examined many important measures not studied in other studies of
late-stage HIV disease presentation in sub-Saharan Africa. Finally,
a small number of HIV-infected participants either did not fully
complete our survey or agree to CD4 count testing, so we cannot
assess their influence on our findings.
In conclusion, we found independent risk factors for
presentation with late-stage HIV disease from diverse domains, including
geographic, economic, demographic, social, and psychosocial.
These can directly inform efforts to improve HIV testing. Such
efforts should focus on various interventions, such as the use of
active mobile testing strategies, financial assistance, or providing
food supplementation, to reduce late-stage disease presentation in
resource-poor settings (Table 4). Simply expanding HIV testing
will not ensure ART-eligible people are enrolled in care or
initiated on ART; innovative approaches are also needed to
improve subsequent linkage to treatment [48,49]. Providing
increased and targeted HIV testing to those at greatest risk for
late-stage HIV disease, and subsequently linking them to HIV care
should reduce AIDS-related morbidity and mortality.
We would like to acknowledge the excellent work and valuable
contributions of our research staff and nurses. We thank each of the
clinical sites for sharing their enthusiasm and space. We thank The U.S.
Presidents Plan for AIDS Relief (PEPFAR), which provided funding for
HIV care and services, including ART, for the participants in our study.
Finally, we graciously thank all of the men and women who participated in
Conceived and designed the experiments: PKD EL JG DR JNK KAF
RPW IVB. Performed the experiments: PKD GP JG DR IVB. Analyzed
the data: PKD GP EL JG DR JNK SMC LMB KAF RPW IVB.
Contributed reagents/materials/analysis tools: EL SMC. Wrote the paper:
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