DOI: 10.1111/hiv.

12529
2017 British HIV Association HIV Medicine (2017)
SHORT COMMUNICATION

Epidemiology of tuberculosis and HIV coinfections in

Singapore, 2000 2014
K Nandar,1 LW Ang,1 J Tey,1 L James,1 KM Kyi Win,2 CBE Chee,2 OT Ng,2 JL Cutter1 and YT Wang2
1
Ministry of Health, Singapore, and 2Tan Tock Seng Hospital, Singapore

Cross-matching of records between Singapores tuberculosis and HIV registries showed that 3.3%
of individuals with tuberculosis (TB) were coinfected with HIV (2000 2014), the TB incidence
among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections
were diagnosed within 1 month of each other. The findings supported joint prevention
programmes for early diagnosis and treatment.
Keywords: coinfection, demography, HIV infections, registries, Singapore, tuberculosis
Accepted 3 May 2017

Introduction HIV/AIDS cases are notified to the National Public

Tuberculosis (TB) and HIV pose a dual epidemic threat
to global health [1]. Trends of these two diseases in
Singapore indicate that TB and HIV coinfection poses a
potential public health threat. The TB incidence rate in
Singapore residents has markedly declined in the past
decades, and is the lowest rate among South-East Asian
countries [2]. However, it is still much higher than that
in many developed countries [3]. The HIV prevalence
among Singaporean adults ( 15 years old) in 2014 was
0.15% [4] compared to 0.3% and 0.1% in the South-
East Asia and Western Pacific regions, respectively [5].
In our study, we describe the demographic and clinical
characteristics of TB and HIV coinfections in Singapore,
and discuss the implications related to public health pol-
icy and disease surveillance.
Methods
In Singapore, TB and HIV are notifiable under the Infec-
tious Diseases Act. All suspected and confirmed TB cases
are notified to the national TB registry within 72 hours
of starting TB treatment and/or receiving laboratory con-
firmation by acid-fast bacillus smear followed by
mycobacterial culture [2]. First-line drug-susceptibility
testing (DST) (i.e. susceptibility to streptomycin, rifampi-
cin, isoniazid and ethambutol) is performed for positive
TB isolates. Isolates resistant to isoniazid and/or rifampi-
cin are subjected to second-line DST.
Correspondence: Dr Khine Nandar, Ministry of Health, 16 College Road,
Singapore 169854. Tel: +65 6325 5679; fax: +65 6325 4679; e-mail:
khine_nandar@moh.gov.sg
Health Unit of the Ministry of Health (MOH). HIV screen-
ing is performed using enzyme immunoassays or rapid
diagnostic tests, followed by a confirmatory western blot
test for positive results.
Both registries contain information on demographics,
such as age at diagnosis, gender, ethnicity, occupation,
country of birth and year of immigration to Singapore.
The TB registry tracks the progress and treatment out-
come of each case, while the HIV registry captures CD4
cell counts, stage of HIV infection at diagnosis and mode
of HIV detection.
Our study received ethics approval from the Singapore
National Healthcare Group Domain Specific Review Board
(NHG DSRB reference number 2015/00702). We retro-
spectively matched records between the HIV registry from
1985 to 2014 and the TB registry from 2000 to 2014. For
TB cases with more than one notification, the first
episodes were included in the study. The date of TB diag-
nosis is the earliest of the following dates: date treatment
started, registration date, date of first positive smear, and
date of first positive culture.
This study was confined to Singapore citizens and per-
manent residents. We defined TB and HIV coinfections as
cases where the patient was diagnosed with HIV infection
within 1 year of TB diagnosis, or diagnosed with HIV infec-
tion followed by TB. Of 798 matched records, 34 TB cases
in which the patient had an HIV diagnosis > 1 year after
TB diagnosis were excluded; none of them had multi-drug-
resistant TB (MDR-TB), i.e. resistance to both rifampicin
and isoniazid. Data analysis was confined to 764 coinfected
cases. The TB incidence density rate (IDR) was defined as
the number of TB cases occurring per 100 person-years of
observation with follow-up censored at TB diagnosis, death
or 31 December 2014, whichever was the earliest date.

1
2 K Nandar et al.
A chi-square test or Fishers exact test was used to
analyse differences between groups where appropriate.
SPSS software, version 23 (IBM Corp., Armonk, NY, USA)
was used for statistical analyses. A P-value < 0.05 was
considered statistically significant.
Results
Between 2000 and 2014, a total of 23 150 TB cases
(15 259 laboratory confirmed and 7891 clinically diag-
nosed) were reported, of which 764 (3.3%) were HIV posi-
tive (annual range, 2.6 4.7%) (Fig. 1). Adults aged
between 30 and 49 years contributed 55.5% of coinfec-
tions, while men and Chinese contributed 94.1% and
82.1%, respectively. Younger age, male gender, Chinese
ethnicity and being Singapore-born were significantly
associated with coinfection (all P < 0.0005) (Table 1).
About half (52.5%) of coinfected cases had both infec-
tions diagnosed within 1 month; 49.5% had only pul-
monary TB; and 95.3% were newly diagnosed with TB.
Compared with non-HIV-infected cases with TB, TB and
HIV-coinfected cases were more likely to have extrapul-
monary TB (EPTB) or both pulmonary and extrapul-
monary TB, and a higher proportion were newly
diagnosed with TB (all P < 0.0005). About 29.7% of EPTB
cases were laboratory confirmed. The lymphatic system
and pleura were the most common sites of infection in
coinfected cases with EPTB and non-HIV-infected cases
with EPTB, respectively. First-line DSTs were conducted
in 650 TB and HIV-coinfected cases and 16 358 non-
HIV-infected cases with TB in whom Mycobacterium
tuberculosis complex (MTC) was detected, and resistance
to isoniazid without rifampicin resistance was detected in
3.8% and 2.7% of coinfected cases and non-HIV-infected
Fig. 1 Tuberculosis (TB) incidence per 100 000 population and proportion of TB and HIV coinfections by year of TB notification in Singapore,
2000 2014.
2017 British HIV Association
cases with TB, respectively (P = 0.088). The proportion of
cases with MDR-TB was significantly higher in coinfected
cases (0.9%) than in non-HIV-infected TB cases (0.4%)
(P = 0.04) (Table 1).
Between 1985 and 2014, a total of 6685 cases of HIV
infection were reported; 603 of them had a TB diagnosis
on the same day or later, giving a TB IDR of 1.65 per
100 person-years. The proportion of coinfections among
HIV-infected cases was highest in 2001, at 24.1%, and
thereafter it declined continuously to 5.9% in 2014 (test
for trend, P < 0.0005).
Compared with non-TB infected HIV cases, TB and
HIV-coinfected cases were significantly more likely to
have advanced HIV infection and a CD4 count
< 200 cells/lL. They were more likely to have an HIV
diagnosis through medical care and screening than non-
TB infected HIV cases (82.1% versus 69.6%, respectively)
and to have been infected via heterosexual contact
(79.3% versus 56.5%, respectively) and injecting drug use
(4.6% versus 1.4%, respectively) (all P < 0.0005)
(Table 1).
Discussion
Our study is one of the first in South East Asia to report
TB and HIV coinfections by cross-matching 15 years of
data from two national registries [6,7]. The proportion of
coinfections (2.9%) among TB cases between 2012 and
2014 was lower compared with that of countries in Asia
with a high TB burden [8]. No particular trend in the
annual proportion of coinfections was observed. The
overall TB IDR among HIV-infected patients, at 1.65 per
100 person-years, was similar to that reported in the
Asia-Pacific region (1.98 per 100 person-years) [9].
HIV Medicine (2017)
 TB/HIV coinfections in Singapore 3

Table 1 Characteristics of tuberculosis (TB) and HIV-coinfected cases, non-HIV-infected TB and non-TB-infected HIV cases in Singapore

TB and HIV-coinfected Non-HIV-infected TB Non-TB-infected HIV

cases (n = 764) cases (n = 22 386) cases (n = 5921)
Characteristic n (%) n (%) n (%)

Gender
Male 719 (94.1) 15 578 (69.6) 5357 (90.5)
Female 45 (5.9) 6808 (30.4) 564 (9.5)
Ethnic group
Chinese 627 (82.1) 16 185 (72.3) 4643 (78.4)
Malay 101 (13.2) 4218 (18.8) 790 (13.3)
Indian 26 (3.4) 1376 (6.2) 300 (5.1)
Other 10 (1.3) 607 (2.7) 188 (3.2)
Time of TB diagnosis
Before HIV diagnosis
1 12 months 47 (6.2)
< 1 month 114 (14.9)
After HIV diagnosis
< 1 month* 287 (37.6)
1 3 months 46 (6.0)
4 6 months 26 (3.4)
7 12 months 27 (3.5)
13 24 months 36 (4.7)
25 48 months 60 (7.9)
> 48 months 121 (15.8)
All TB cases
Age at TB diagnosis
0 9 years 1 (0.1) 164 (0.7)
10 19 years 0 (0.0) 650 (2.9)
20 29 years 35 (4.6) 1928 (8.6)
30 39 years 151 (19.8) 2536 (11.3)
40 49 years 273 (35.7) 3607 (16.1)
50 59 years 167 (21.9) 4347 (19.4)
60 years 137 (17.9) 9154 (40.9)
Period of TB notification
20002002 156 (20.4) 4818 (21.5)
20032005 142 (18.6) 4342 (19.4)
20062008 166 (21.7) 4113 (18.4)
20092011 167 (21.9) 4581 (20.5)
20122014 133 (17.4) 4532 (20.2)
Born in Singapore
Yes 726 (95.0) 18 535 (82.8)
No 38 (5.0) 3851 (17.2)
Clinical characteristics
Site of disease
Pulmonary alone 378 (49.5) 17 656 (78.9)
Extrapulmonary alone 131 (17.1) 2933 (13.1)
Both pulmonary and extrapulmonary 255 (33.4) 1797 (8.0)
Category of TB
New 728 (95.3) 20 625 (92.1)
Relapse 36 (4.7) 1761 (7.9)

TB and HIV-coinfected Non-HIV-infected cases

cases (n = 650) with TB (n = 16 358)
n (%) n (%)

Patients with TB with MTC detected

Drug resistance
INH but not RMP 25 (3.8) 446 (2.7)
INH and RMP 6 (0.9) 65 (0.4)
RMP but not INH 4 (0.6) 23 (0.1)
Other drugs 21 (3.2) 463 (2.8)

2017 British HIV Association HIV Medicine (2017)

4 K Nandar et al.

Table 1 (Continued )

TB and HIV-coinfected Non-HIV-infected TB Non-TB-infected HIV

cases (n = 764) cases (n = 22 386) cases (n = 5921)
Characteristic n (%) n (%) n (%)

All HIV-infected patients

Age at HIV diagnosis
0 9 years 1 (0.1) 30 (0.5)
10 19 years 3 (0.4) 68 (1.2)
20 29 years 60 (7.9) 1080 (18.2)
30 39 years 173 (22.6) 1802 (30.4)
40 49 years 242 (31.7) 1508 (25.5)
50 59 years 162 (21.2) 902 (15.2)
60+ years 123 (16.1) 531 (9.0)
Period of HIV notification
19851999 82 (10.7) 1054 (17.8)
20002002 151 (19.8) 546 (9.2)
20032005 135 (17.7) 735 (12.4)
20062008 147 (19.2) 1091 (18.4)
20092011 117 (15.3) 1248 (21.1)
20122014 132 (17.3) 1247 (21.1)
Stage of HIV diagnosis
Not late stage 202 (26.4) 3057 (51.6)
Late stage 562 (73.6) 2864 (48.4)
Baseline CD4 count
< 50 cells/lL 177 (23.2) 1121 (18.9)
50 199 cells/lL 161 (21.1) 872 (14.7)
200 500 cells/lL 76 (9.9) 1367 (23.1)
> 500 cells/lL 19 (2.5) 422 (7.1)
Unknown 331 (43.3) 2139 (36.1)
Mode of HIV detection
Medical care and screening 627 (82.1) 4120 (69.6)
Own request 33 (4.3) 733 (12.4)
Contact tracing 24 (3.1) 283 (4.8)
Prisons/Drug Rehabilitation Centre/halfway house 34 (4.5) 209 (3.5)
Life insurance 12 (1.6) 120 (2.0)
Blood donation 6 (0.8) 104 (1.7)
Other 20 (2.6) 318 (5.4)
Unknown 8 (1.0) 34 (0.6)
Mode of HIV transmission
Heterosexual 606 (79.3) 3346 (56.5)
Homosexual/bisexual 105 (13.7) 2274 (38.4)
Injecting drug use 35 (4.6) 81 (1.4)
Blood transfusion 0 (0.0) 3 (0.1)
Renal transplant overseas 0 (0.0) 5 (0.1)
Perinatal (mother to child) 1 (0.1) 30 (0.5)
Uncertain 17 (2.2) 182 (3.1)

INH, isoniazid; MTC, Mycobacterium tuberculosis complex; RMP, rifampin.

*Includes 56 patients diagnosed with TB and HIV on the same day.

The patient category is defined as follows: new, patient who never previously received treatment for > 1 month; relapse, patient who previously com-
pleted treatment or was treated and declared cured prior to developing active TB again.

Late-stage HIV infection was defined as having a CD4 count of < 200 cells/lL or developing AIDS-defining opportunistic infections at first diagnosis
or within 1 year after HIV diagnosis.

The proportion of coinfections among HIV cases plum-
meted from 24.1% in 2001 to 5.9% in 2014. In the same
period, among all coinfections, the annual proportion of
coinfections diagnosed within 1 month of each other
increased, while that of cases having a TB diagnosis more
than 1 month after an HIV diagnosis decreased. These
findings suggest that the significant decline in the pro-
portion of coinfections among HIV-infected patients
could be attributable to early HIV diagnosis and highly
active antiretroviral therapy (HAART).
Singapore-born residents constituted the vast majority
of coinfected cases, unlike some Europe countries where
foreign-born individuals have played an increasingly
important role in the TB and HIV coinfection epidemiol-
ogy [10,11]. However, a local study reported increases in
the number and proportion of foreign-born individuals
with TB among long-term pass holders and permanent
residents between 2000 and 2009 [12]. The impact of TB
epidemiology on TB and HIV coinfections should be
monitored closely.

2017 British HIV Association HIV Medicine (2017)


More than a third (39.8%) of coinfected patients were
aged 50 years, and these patients were reported to have
lower CD4 counts at HIV diagnosis and a higher rate of
active TB, and were more likely to have adverse clinical
outcomes [13,14]. Our findings reinforce the need to
increase HIV awareness and improve prevention measures
and screening services in this older age group.
About half of coinfected patients (53%) had diagnoses
of TB and HIV infection within 1 month of each other.
At the Tuberculosis Control Unit (TBCU), where nearly
70% of all Singapore residents with TB undergo treat-
ment, more than 90% of patients with TB were screened
for HIV between 2009 and 2011 (unpublished data by
TBCU). However, the HIV screening rate at other TB treat-
ment centres remained low, ranging between 7% and
56%. The take-up rate of HIV testing among patients with
TB could be improved, especially at other TB treatment
centres.
Compared with non-TB-infected HIV cases, coinfected
cases were more likely to have advanced HIV infection at
the time of HIV diagnosis. To encourage HIV testing for
early detection, various measures have been implemented
in Singapore, such as increasing the numbers of anony-
mous HIV testing sites and services offering rapid HIV
testing, and provision of antenatal screening and in-
patient voluntary opt-out HIV testing.
Our study reported a low level of drug-resistant TB
among coinfected cases (3.8%). However, Singapore is sit-
uated in a highly TB prevalent region and is a travel hub,
with high traffic of visitors from countries with a high
MDR-TB burden. Ongoing surveillance for drug-resistant
TB is important to detect changes in local epidemiology.
Our study has a number of limitations. The true extent
of coinfection is likely to be underestimated, as some TB
or HIV infections may not have been diagnosed among
the notified cases. Clinical information on viral load and
use of HAART in coinfected cases was not available. As
information on screening for latent TB and isoniazid pro-
phylaxis was not available, we could not comment on TB
services used by 32% of coinfected patients who devel-
oped TB more than 6 months after HIV diagnosis.
In conclusion, our findings reinforce the existing recom-
mendations that all cases with a new TB diagnosis should
be tested for HIV at the time of TB diagnosis and all cases
newly diagnosed with HIV infection should be screened for
latent and active TB for early diagnosis and treatment to
combat the dual threat posed by these epidemics.
Acknowledgements
We wish to thank the Tuberculosis Control Unit, Tan Tock
Seng Hospital for providing TB data, the National Public
2017 British HIV Association
TB/HIV coinfections in Singapore 5
Health Unit, Ministry of Health, Singapore for providing
HIV data and cross-matching the data from the two reg-
istries, and the Policy and Control Branch, Communicable
Diseases Control Division, Ministry of Health, Singapore for
their input on policies and measures for prevention and
control of TB and HIV infections in Singapore.
Funding: This research did not receive any specific
grant from funding agencies in the public, commercial,
or not-for-profit sectors.
References
1 Joint United Nations Programme on HIV/AIDS (UNAIDS).
Frequently Asked Questions About Tuberculosis and HIV.
Available at http://data.unaids.org/pub/factsheet/2006/tb_
hiv_qa.pdf (accessed 2 June 2016)
2 Suhana S, Lim J, Ang LW, Ooi PL, Cutter J. Changing
epidemiology of tuberculosis in Singapore, 20022011.
Epidemiol News Bull 2012; 38: 4754.
3 World Health Organization. Global Tuberculosis Report 2015.
WHO, 2015. Available at http://apps.who.int/iris/bitstream/
10665/191102/1/9789241565059_eng.pdf?ua=1 (accessed 2
June 2016)
4 Joint United Nations Programme on HIV/AIDS (UNAIDS):
2015 Progress reports submitted by countries. Global AIDS
Response Progress Reporting (GARPR) 2014 Country
Progress Report Singapore. Available at http://www.unaids.
org/sites/default/files/country/documents/SGP_narrative_
report_2015.pdf (accessed on 9 Apr 2017)
5 World Health Organization (WHO): Global Health
Observatory data repository. Prevalence of HIV among adults
aged 15 to 49 Estimates by WHO region. Available at http://
apps.who.int/gho/data/view.main.22500WHOREG?lang=en
(accessed on 9 Apr 2017)
6 Trinh QM, Nguyen HL, Do TN et al. Tuberculosis and HIV
co-infection in Vietnam. Int J Infect Dis 2016; 46: 5660.
7 Lee CH, Hwang JY, Oh DK et al. The burden and
characteristics of tuberculosis/human immunodeficiency virus
(TB/HIV) in South Korea: a study from a population database
and a survey. BMC Infect Dis 2010; 10: 66.
8 Trinh QM, Nguyen HL, Nguyen VN, Nguyen TV, Sintchenko
V, Marais BJ. Tuberculosis and HIV co-infection-focus on the
Asia-Pacific region. Int J Infect Dis 2015; 32: 170178.
9 Zhou J, Elliott J, Li PC et al. Risk and prognostic significance
of tuberculosis in patients from The TREAT Asia HIV
observational database. BMC Infect Dis 2009; 9: 46.
10 Velasco M, Castilla V, Cervero M et al. COMESEM cohort.
The changing pattern of tuberculosis and HIV co-infection in
immigrants and Spaniards in the last 20 years. HIV Med
2008; 9: 227233.
11 Camoni L, Regine V, Boros S, Salfa MC, Raimondo M,
Suligoi B. AIDS patients with tuberculosis: characteristics
HIV Medicine (2017)
6 K Nandar et al.
and trend of cases reported to the National AIDS Registry
in Italy1993-2010. Eur J Public Health 2013; 23: 658663.
12 Kyi Win KM, Chee CB, Shen L, Wang YT, Cutter J.
Tuberculosis among foreign-born persons, Singapore, 2000-
2009. Emerg Infect Dis 2011;17:517519.
13 Tey JSH, Ang LW, Tay J et al. Determinants of late-stage
HIV disease at diagnosis in Singapore, 1996 to 2009. Ann
Acad Med Singapore 2012; 41: 194199.
2017 British HIV Association
14 Lee LK, Seinn OPP, Ng OT, Lee CC, Leo YS, Chua AC. Older
age at initial presentation to human immunodefi ciency virus
(HIV) care and treatment at the Communicable Disease
Centre (CDC) in Singapore, 2006 to 2011. Ann Acad Med
Singapore 2012; 41: 577580.
HIV Medicine (2017)