Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Effectiveness of isoniazid preventative therapy in reducing incidence of active tuberculosis among people living with HIV/AIDS in public health facilities of Addis Ababa, Ethiopia: a historical cohort study

  • Mahlet Semu1,
  • Teferi Gedif Fenta2Email author,
  • Girmay Medhin3 and
  • Dawit Assefa4
BMC Infectious Diseases201717:5

https://doi.org/10.1186/s12879-016-2109-7

Received: 19 April 2016

Accepted: 10 December 2016

Published: 3 January 2017

Abstract

Background

Human Immunodeficiency Virus (HIV) pandemic has exacerbated tuberculosis disease especially in Sub-Saharan African countries. The World Health Organization (WHO) and Joint United Nations Program on HIV/AIDS (UNAIDS) have recommended Isoniazid Preventive Therapy (IPT) for HIV infected patients to reduce the burden of tuberculosis (TB). Ethiopia has been implementing IPT since 2007. However, effectiveness of IPT in averting occurrence of active tuberculosis among HIV infected patients has not been assessed.

Methods

Retrospective cohort study was employed using secondary data from public health institutions of Addis Ababa. Descriptive statistics and Generalized Linear Model based on Poisson regression was used for data analysis.

Results

From 2524 HIV infected patients who were followed for 4106 Person-Years, a total of 277 incident Tuberculosis (TB) cases occurred. TB Incidence Rate was 0.21/100 Person-Year, 0.86/100 Person-Year & 7.18/100 Person-Year among IPT completed, in-completed and non-exposed patients, respectively. The adjusted Incidence Rate Ratio (aIRR) among IPT completed vs. non-exposed patients was 0.037 (95% CI, 0.016-0.072). Gender, residence area, employment status, baseline WHO stage of the disease (AIDS) and level of CD4 counts were identified as risk factors for TB incidence. The aIRR among patients who took Highly Active Anti- Retroviral Therapy (HAART) with IPT compared to those who took HAART alone was 0.063 (95% CI 0.035-0.104). IPT significantly reduced occurrence of active TB for 3 years.

Conclusions

IPT significantly reduced tuberculosis incidence by 96.3% compared to IPT non-exposed patients. Moreover concomitant use of HAART with IPT has shown a significant reduction in tuberculosis incidence by 93.7% than the use of HAART alone. Since IPT significantly protected occurrence of active TB for 3 years, its implementation should be further strengthened in the country.

Keywords

IPT Incidence of active TB TB/HIV co-infection Ethiopia

Background

Tuberculosis (TB) and Human Immunodeficiency virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) are major public health threat [13]. Among HIV infected patients, TB is the most frequent life threatening opportunistic disease, even in those receiving Highly Active Antiretroviral Therapy (HAART) and it has been shown to be a leading cause of death [2, 4, 5]. HIV infection is also the strongest risk factor for TB disease [3]. In 2011, globally there were 34 million HIV infected patients and at least one-third of these had latent TB & 1.1 million of them developed new TB infection, of these around 79% of patients were from Sub-Saharan African countries, indicating that HIV is fueling the TB epidemics in the region [5]. In Ethiopia like many of the developing countries, TB has created major burden to the health care system due to its linkage with HIV/AIDS epidemics [6]. In 2010, TB incidence in HIV-positive patients was 48 (27–76) per 100,000 population and the prevalence of TB including among HIV positives was 572(265–947) per 100,000 population [7].

Since 1998, WHO and the Joint United Nations Program on HIV/AIDS (UNAIDS) have recommended Isoniazid Preventive Therapy (IPT) as one of the key interventions in the comprehensive HIV/AIDS care strategy to reduce the burden of TB among HIV infected patients [8]. According to WHO [2], IPT given to HIV infected patients without TB disease reduces the risk of developing TB by 33–67% for up to 48 months. Regarding the concomitant use of HAART with IPT, a meta-analysis led by WHO found out that HAART reduces the individual risk of TB disease by 65%, irrespective of the CD4 cell count but recent evidence has shown that the combined use of IPT and HAART among HIV infected patients significantly reduces the incidence of TB by up to 97% [9].

In Ethiopia, IPT provision for HIV infected patients is recommended by the national TB/HIV Collaborative Activities guideline and its implementation has been started since 2007[10]. However, the effectiveness of IPT in reducing the burden of active TB among HIV infected patients relative to those who did not take or discontinued has not been assessed yet. Moreover the clinical and programmatic factors affecting the treatment outcome among those who took have not been clearly identified. Therefore, this study assessed the effectiveness of the provision of IPT for HIV infected patients in averting occurrence of TB in the Ethiopian context.

Methods

A multi-centered retrospective cohort study design was employed using secondary data from 14 public health facilities giving ART service in Addis Ababa. From seven facilities which were giving IPT service between 2007 and January 2010, all adult HIV positive patients (1264) who were either on HAART or Pre-ART and exposed to IPT in the study period and who were followed for at least a year were included as IPT exposed patients. All IPT discontinued patients regardless of their follow up time were also included. For comparison, equivalent number of non- IPT exposed patients who were on HIV care management for 1 or more years were sampled from randomly selected facilities which were not providing IPT till January 2010. All pediatric HIV positive patients regardless of whether they took/did not take IPT in the study period set, and all transferred in patients were excluded from this study. The patient charts from each facility were selected by random sampling method. A structured data abstraction format was used to collect information from medical records/chart of patients and the data was collected from July 1 to August 31, 2012. The data was entered and processed using SPSS version 16 statistical software. Descriptive statistics for patient characterization, Generalized Linear Model based on Poisson distribution to get incidence rate and incidence rate ratio, nonparametric test and Chi Square test were used for statistical analysis.

Results

A total of 2528 patients’ charts were reviewed and four charts were with incomplete information and hence only 2524 charts were included in analysis. Of these, 1582(62.7%) were female and their mean age was 34.9 years. Majority were married and from Orthodox family. A significant proportion (44.9%) was un-employed. There is significant difference in level of education, marital status and employment status (Table 1).
Table 1

Socio-demographic characteristics of patients at enrollment for chronic HIV care in public health facilities of Addis Ababa, during 2007-June 2012

Socio-demographic profile at enrollment for HIV care (N = 2524)

IPT Exposed

N (%)

IPT Non-exposed

N (%)

Total

N (%)

Chi-square

P value

Sex

 Male

473(37.4)

469(37.2)

942(37.3)

0.918

 Female

791(62.6)

791(62.8)

1582(62.7)

 

Age in years (mean = 34.9, SD = 9.1)

 <30

421(33.3)

557(44.2)

978(38.7)

0.150

 30–39

408(32.3)

412(32.7)

820(32.5)

 

 40–49

283(22.4)

247(19.6)

530(21)

 

 >50

152(12)

44(3.5)

196(7.8)

 

Marital status

 Single

318(25.2)

288(22.9)

606(24)

0.000

 Married

584(46.2)

551(43.7)

1135(45)

 

 Widowed

189(15)

195(15.5)

384(15.2)

 

 Separated

157(12.4)

165(13.1)

322(12.8)

 

 Divorced

16(1.3)

61(4.8)

77(3.1)

 

Level of Education

 No formal education

248(19.6)

276(21.9)

524(20.8)

0.004

 Primary completed

507(40.1)

447(35.5)

954(37.8)

 

 Secondary completed

473(37.4)

473(37.5)

946(37.5)

 

 Tertiary completed

36(2.8)

64(5.1)

100(4)

 

Religion

 Orthodox

979(77.5)

1023(81.2)

2002(79.3)

0.197

 Muslim

98(7.8)

177(14)

275(10.9)

 

 Protestant

132(10.4)

54(4.3)

236(9.4)

 

 Othersa

5(0.4)

6(0.5)

11(0.4)

 

Employment status

 Non-employed

650(51.4)

483(38.3)

1133(44.9)

0.000

 Self-employed

218(17.2)

247(19.6)

465(18.4)

 

 Government employed

205(16.2)

248(19.7)

453(17.95)

 

 Private

183(14.5)

270(21.4)

453(17.95)

 

 Student

8(0.63)

12(0.95)

20(0.8)

 

Residence place

 Addis Ababa

1230(97.3)

1252(99.4)

2482(98.3)

0.322

 Out of Addis Ababa

34(2.7)

8(0.6)

42(1.7)

 

Average no. of personnel per family

3.15

3.45

3.3

0.092

Average no. of rooms per family

1.35

1.65

1.5

0.593

aCatholic and Joba

All of the patients were Pre-ART at the time of enrollment for chronic HIV care and the baseline clinical information of the patients is shown in Table 2. Majority of the patients were in stage 3 followed by stage 2, 972 (38.5%) and 833 (33%), respectively. There was significant clinical difference between the two groups.
Table 2

Baseline clinical information of HIV positive patients in public health facilities of Addis Ababa, during 2007-June 2012

Baseline Clinical status (N = 2524)

IPT Exposed

N (%)

IPT Non-exposed

N (%)

Total

N (%)

Chi-square

P value

Initial WHO stage of HIV/AIDS

 Stage 1

357(28.2)

215(17.1)

572(22.7)

0.000

 Stage 2

487(38.5)

346(27.5)

833(33)

 

 Stage 3

392(31)

580(46)

972(38.5)

 

 Stage 4

28(2.3)

119(9.4)

147(5.8)

 

Baseline CD4cells count/μl(mean = 230, SD = 176.9)

 ≤200

570(45.1)

807(64)

1377(54.6)

0.000

 >200

694(54.9)

453(36)

1147(45.4)

 

Initial body weight in Kg (mean = 53.8, SD = 9.7)

 <50

304(24.1)

554(43.8)

858(34)

0.009

 50–59

628(49.7)

418(33.1)

1046(41.4)

 

 60–69

208(16.5)

214(17)

422(16.7)

 

 >69

124(9.8)

74(5.9)

198(7.8)

 

TB screeneda

 Positive

0

40(3.2)

40(1.6)

 

 Negative

1264(100)

1220(96.8)

2484(98.4)

 

 On CPT

 Yes

1259(99.6)

1205(95.6)

2464(97.6)

0.000

 No

5(0.4)

55(4.4)

60(2.4)

 

OIs diagnosed

 None

1082(85.6)

907(71.9)

1989(78.8)

0.000

 Bacterial infections

11(0.87)

164(13)

175(6.9)

 

 Viral infections

25(0.08)

88(6.9)

113(4.5)

 

 Fungal infections

38(3)

129(10.2)

167(6.6)

 

 Viral & bacterial infections

20(1.6)

13(1.03)

33(1.3)

 

 Bacterial & fungal infections

11(0.87)

8(0.63)

19(0.8)

 

 Fungal & viral infections

8(0.6)

12(0.95)

20(0.8)

 

aA patient is TB positive, if he/she has at least two of these signs/symptoms: Weight loss greater than or equal to 5% of the initial weight, coughing for 2 weeks, night sweat, night-mar, Loss of appetite

As shown in Table 3, from all patients for whom their charts were reviewed, 2046 (81.1%) had initiated HAART during their follow up; of whom 945 (46.2%) of them were WHO stage 3.
Table 3

Clinical information of patients who were unheard follow upinpublic health facilities of Addis Ababa, during 2007-June 2012

Clinical information when ART initiated (N = 2046)

IPT exposed

N (%)

IPT Non-exposed

N (%)

N (%)

Chi-square

P value

WHO stage of HIV/AIDS

 Stage 1

151(16.02)

138(12.5)

289(14.1)

0.000

 Stage 2

367(39)

294(26.6)

661(32.3)

 

 Stage 3

394 (41.8)

551(49.9)

945(46.2)

 

 Stage 4

30 (3.18)

121(11.0)

151(7.4)

 

CD4cells count/μl(mean = 151.2, SD = 84.9)

 ≤200

537 (37.9)

1020(92.4)

1557(76.1)

0.000

 >200

263 (27.9)

226(20.5)

489(23.9)

 

Weight in Kg (mean = 53.2, SD = 9.5)

 <50

241(25.6)

506(45.8)

747(36.5)

0.011

 50–59

479(44.2)

366(33.1)

845(41.3)

 

 60–69

164 (17.4)

164(14.9)

328(16.0)

 

 >69

58 (6.2)

68(6.2)

126(6.2)

 

TB screened

 Yes

942(100)

1100(99.6)

2042(99.8)

0.64

 No

0

4(0.4)

4(0.2)

 

CPT adherence

 Good

791(84)

1096(99.3)

2032(99.6)

0.046

 Fair

3(.32)

6(0.5)

9(0.3)

 

 Poor

3(.32)

2(0.2)

5(0.2)

 

ART adherence

 Good

937(99.5)

1100(99.6)

2037(99.6)

0.124

 Fair

5(0.53)

2(0.2)

7(0.3)

 

 Poor

0

2(0.2)

2(0.1)

 

OIs after ART initiated

 None

937(99.5)

1052(95.3)

1989(97.21)

0.000

 Fungal

3(.32)

20(1.8)

23(1.12)

 

 Viral

0

12(1.0)

12(0.5)

 

 Bacterial

0

12(1.0)

14(0.7)

 

 Bacterial & fungal

0

4(0.4)

4(0.2)

 

 Othersa

0

4(0.4)

4(0.2)

 

aProtozoal, viral & bacterial & fungal & viral infections

Out of 1264 patients who were given IPT, completion rate was 975(77.1%). Among IPT exposed patients; 942(74.5%) were on HAART and of these 738(78.3%) completed IPT (Table 4).
Table 4

Profile of IPT exposed patients inpublic health facilities of Addis Ababa, during 2007-June 2012

Profile (N = 1264)

N (%)

Chi-square

P-value

 Male

473(37.4%)

 

 Female

791(62.6%)

 

TB screened & tested negative

1264(100%)

 

Currently on HAART

942(74.5%)

 

Pre-ART

322(25.5%)

 

HAART initiated before IPT

578(61.3%)

 

HAART initiated after IPT

364(38.7%)

 

IPT completed

975(77.1%)

 

IPT discontinued

289(22.9%)

 

On HAART + IPT completed

738(78.3%)

0.094

Pre-ART + IPT completed

237(73.6%)

On HAART + IPT in-completed

204(21.7%)

0.08

Pre-ART + IPT in-completed

85(26.4%)

 

Male IPT completed

359(75.9%)

0.459

Female IPT completed

616(77.8%)

Took B6 together with INH

581(46%)

 

No IPT side effects

1254(99.2%)

 
Among 2524 HIV-infected patients who were followed for 4106 P-Y, 277 incident TB cases occurred, making the overall incidence of 6.7/100P-Y. Among IPT completed group, incidence rate was 0.21/100PY, while in IPT non-exposed patients; it was 7.18/100P-Y. Incidence of TB was found to be associated with sex, employment status, baseline WHO stage of HIV/AIDS and CD4 count. Completion of IPT showed significant protective effect against occurrence of active TB when compared to IPT non-exposed patients aIRR = 0.037 (CI 95% 0.016-0.072)} (Table 5, Fig. 1).
Table 5

Incidence rate, univariate and multivariate analysis among IPT completed, in-completed and non- exposed patients in public health facilities of Addis Ababa, during 2007-June 2012

Patient profile

Event/P/Y

IR/100P-Y

Crude IRR (95% CI)

Adjusted IRR(95% CI)

Over all

277/4106

6.7

  

IPT completed

7/33.3

0.21

0.03(0.01–0.06)

0.04(0.05–0.07)

IPT in-completed

8/7.8

0.86

0.84(0.36–1.33)

0.89(0.49–1.76)

IPT non-exposed

262/36.49

7.18

1

1

Sex

 Male

138/2822.1

4.89

1.80(1.42–2.28)

1.59(1.20–2.12)

 Female

139/5129.2

2.71

1

1

Age group in year

 <30

103/3038.3

3.39

1

1

 30–39

87/2628.4

3.31

0.98(0.73–1.29)

0.82(0.61–1.11)

 40–49

61/1644.2

3.71

1.09(0.79–1.49)

1.04(0.74–1.47)

 >49

26/637.3

4.08

1.201(0.77–1.82)

1.55(0.95–2.44)

Residence area

 Living out of Addis Ababa

4/135.1

2.96

0.85(0.26–1.99)

0.29(0.09–0.73)

 Living in Addis Ababa

273/7800

3.50

1

1

Religion

 Orthodox

231/6243.2

3.70

0.63(0.20–3.82)

0.29(0.08–1.86)

 Muslim

19/892

2.13

0.36(0.11–2.28)

0.17(0.04–1.13)

 Protestant

25/778.8

3.21

0.55(0.16–3.40)

0.32(0.09–2.12)

 Others*

11/187.7

5.86

1

1

Marital status

 Married

127/3547.5

3.58

0.82(0.46–1.68)

1.22(0.66–2.51)

 Single

72/1889.8

3.81

0.88(0.48–1.81)

1.18(0.63–2.48)

 Widowed

33/1284

2.57

0.59(0.30–1.27)

0.81(0.40–1.76)

 Divorced

35/997.2

3.51

0.81(0.45–1.72)

1.05(0.53–2.27)

 Separated

10/229.9

4.35

1

1

Employment

 Self employed

87/3782.6

2.30

0.03(0.01–0.19)

0.02(0.01–0.12)

 Private Employed

58/1418.1

4.09

0.06(0.02–0.35)

0.03(0.01–0.16)

 Government employed

62/1324.8

4.68

0.07(0.02–0.40)

0.03(0.01–0.19)

 Student

3/66.5

4.51

0.06(0.01–0.48)

0.01(0.002–0.101)

 Non- employed

65/1354.2

4.80

1

1

Educational level

 None educated

42/1707.3

2.46

0.65(0.35–1.33)

1.25(0.62–2.70)

 Primary Completed

106/3028.6

3.50

0.93(0.52–1.83)

1.69(0.89–3.49)

 Secondary Completed

118/2920.8

4.04

1.07(0.60–2.10)

1.76(0.97–3.55)

 Tertiary completed

11/291

3.78

1

1

House Hold size/room no.

  

0.99(0.89–1.09)

0.98(0.88–1.07)

Baseline WHO stage of HIV/AIDS

 Stage 1 & 2

45/4545.5

0.99

0.14(0.10–0.19)

0.23(0.16–0.31)

 Stage 3 & 4

232/3381.9

6.86

 

1

Baseline CD4 cells/μl

    

 ≤200

211/4169.9

5.06

2.89(2.21–3.85)

1.36(1.02–1.84)

 >200

66/3771.4

1.75

  

Baseline weight in Kg

 ≤49

113/2646.4

4.27

1.88(1.12–3.43)

1.63(0.93–3.05)

 50–59

108/3343.7

3.23

1.42(0.85–2.59)

1.19(0.69–2.22)

 60–69

42/1333.3

3.15

1.39(0.78–2.64)

1.06(0.59–2.03)

 >69

14/616.7

2.27

1

1

Baseline OIs

 Yes

194/6278.3

3.09

0.62(0.48–0.80)

1.24(0.95–1.63)

 No

83/1660

5.00

1

1

CPT adherence

    

 Good

271/7765

3.49

0.99(0.48–2.51)

0.92(0.44–2.37)

 Fair, Poor & no CPT

2/56.8

3.52

1

1

*others include: catholic, johoba and non belivers

Fig. 1

Incidence rate among IPT completed, in-completed and non- exposed patientsin public health facilities of Addis Ababa, during 2007-June 2012

Similarly, as shown in Table 6 and Fig. 2, those patients who took IPT with HAART had TB incidence rate of 0.42/100P-Y and among patients who took HAART alone, the incidence was 7.83/100P-Y. The concomitant use of IPT with HAART revealed significant protective effect on occurrence of active TB compared to HAART alone {aIRR =0.063(95% CI 0.035-0.104). Among IPT exposed patients, those who took IPT with HAART had lesser incidence than those who took IPT before initiating HAART {aIRR = 0.158(95% CI 0.039- 0.555)}.
Table 6

IR & IRR among patients who took HAART with or without IPT in public health facilities of Addis Ababa, during 2007-June 2012

Therapy (N = 1842)

IR/100P-Y

aIRR(95% CI)

 IPT with HAART

0.42

0.063(0.035–0.104)

 HAART only

7.83

1

IPT initiation time with HAART

 Took IPT with HAART

0.2

0.158(0.039–0.555)

 Took IPT before initiating HAART

0.75

1

Fig. 2

IR among patients who took HAART with IPT in public health facilities of Addis Ababa, during 2007-June 2012

As shown in Table 7, there was significant CD4 and weight changes among IPT-HAART treated patients.
Table 7

Statistical analysis of clinical data among patients who took HAART with IPT in public health facilities of Addis Ababa, during 2007-June 2012

Variables

N

Mean Rank

P- value

Weight after completing IPT – weight at enrollment

Negative Ranks

160a

410.64

 

Positive Ranks

701b

435.65

0.000

Ties

114c

  

Total

975

  

CD4 after completing IPT - CD4 at enrollment

Negative Ranks

253d

546.73

 

Positive Ranks

702e

453.23

0.000

Ties

21f

  

Total

976

  

aWeight when completing IPT < weight when starting IPT

bWeight when completing IPT > weight when starting IPT

cWeight when completing IPT = weight when starting IPT

dCD4 when completing IPT < CD4 when starting IPT

eCD4 when completing IPT > CD4 when starting IPT

fCD4 when completing IPT = CD4 when starting IPT

The median duration of follow- up was 40 months (inter-quartile range, 28–52 months). From those who completed IPT, active TB has occurred between 6 and 28 months duration. Almost 50% of patients who completed IPT developed active TB at 19thmonth; while in non-exposed patients TB occurred within a month time of enrollment (Table 8).
Table 8

Month of occurrence of active TB among IPT completed, in-completed & non-exposed patients in public health facilities of Addis Ababa, during 2007-June 2012

Variables

No of patients active TB diagnosed

Minimum month TB occurred

Maximum month TB occurred

Mean month TB occurred

Standard Deviation

Median

Month TB occurred among IPT completed patients

7

6

28

16.7

8.4

19

Month TB occurred among patients who discontinued IPT

8

0

35

9.6

14.8

0

Month TB occurred among IPT non-exposed

262

0

65

8.1

13.3

1

As shown in Table 9, IPT completers were significantly protected for 3 years {aIRR = 0.04 (95% CI (0.02-1.74)} compared to IPT in-completed and non-exposed patients.
Table 9

TB incidence in month interval among IPT completed, in-completed & non-exposed patients in public health facilities of Addis Ababa, during 2007-June 2012

Follow up month

IPT exposure/completion status

IR/100 P-M (95% CI)

Unadjusted IRR (95% CI)

Adjusted IRR (95% CI)

<6

Completed

0

0

0

In-complete

142.8(17.64–268.07)

1.82(0.65–3.97)

2.125(0.712–5.103)

Non-exposed

78.59(66.9–90.3)

1

1

6–12

Completed

12(1.58–25.58)

0.30(0.06–0.79)

0.03(0.013–1.95)

In-completed

38.71(7.74–69.68)

0.98(0.39–2.02)

1.05(0.32–2.89)

Non-exposed

39.43(34.05–44.82)

1

1

12–24

Completed

6.74(1.35–12.14)

0.29(0.11–0.59)

0.03(0.01–0.74)

In-completed

38.71(7.74–69.68)

1.65(0.65–3.38)

1.61(0.51–4.29)

Non-exposed

23.51(20.48–26.55)

1

1

24–36

Completed

5.98(1.55–10.42)

0.34(0.14–0.66)

0.04(0.02–1.74)

In-completed

9.94(3.05–16.82)

0.56(0.25–1.05)

1.09(0.49–2.54)

Non-exposed

17.87(15.63–20.11)

1

1

37–48

Completed

5.98(1.55–10.42)

0.44(0.186–0.854)

0.74(0.301–1.56)

In-completed

9.94(3.05–16.82)

0.73(0.33–1.37)

0.72(0.314–1.44)

Non-exposed

13.72(12.04–19.56

1

1

>48

Completed

5.98(1.55–10.42)

0.50(0.22–0.99)

0.88(0.36–1.84)

In-completed

9.94(3.05–16.82)

0.84(0.38–1.58)

0.89(0.39–1.76)

Non-exposed

11.88(10.44–13.32)

1

1

Discussion

This retrospective cohort study covering the time from 2007 to June 2012 attempted to assess effectiveness of IPT against active TB in HIV positive adults who were on HIV care in government health facilities of Addis Ababa. Accordingly, the IRs were 0.21/100P-Y, 0.86/100P-Y & 7.18/100P-Y among IPT completed, in-completed & non-exposed patients, respectively. The IR among IPT completed patients was lower when compared with the findings of studies done in different countries [1113]. Moreover, completion of IPT in HIV infected adults significantly reduced TB incidence by 96.3% when compared to non-exposed patients (aIRR = 0.037, 95% CI 0.016-0.072). The present study revealed abetter reduction in TB incidence after IPT in comparison with the results of earlier studies [7, 1416]. Better patient adherence rate, difference in TB burden among the countries or better socioeconomic and clinical status of patients might have contributed to such differences among studies conducted in different countries. Despite the fact that Ethiopia is among high TB burden country, IR among IPT completed patients was comparably lower than studies indicating further the effectiveness of IPT for HIV infected patients. Hence more widespread provision of IPT has the potential to further reduce TB incidence and hence improve quality of life among HIV infected adults in the country.

Among patients who completed IPT, though TB had occurred after 6 months, almost 50% of them developed TB at 19thmonth; while in IPT non-exposed patients, half of patients developed active TB within a month time. The study proved that IPT has been significantly protecting early occurrence of TB during the first 6 months. This finding was comparable to the study done in Thailand where IR among IPT completers was 0 and among non-exposed patients 8.60/100 P-Y [17]. Moreover, the present study indicated that IPT had offered a significant protective effect until 3 years. The durability of protective effect of IPT documented in the present study concurs with the expected level indicated in Ethiopian guideline [10]. It is, however, better than reports from South East Asian and other Sub-Saharan African countries [13, 17, 18].

With regard to risk factors associated with TB occurrence, even though there is significant difference among the two groups in socio-demographic and baseline clinical characteristics, the multivariable analysis revealed significant influence of IPT completion, male sex, employment status, baseline WHO stage of HIV/AIDS (stage 3 & 4) & CD4 cell count (less than 200cells/μl).

Similarly, South African and Namibian studies indicated the influence of clinical factors on the incidence of Tb among HIV patients [13, 16].

Getahun et al. [19] reported that in countries with a high prevalence of HIV, more women than men are diagnosed with TB. But the current study revealed that more males who took IPT were at risk of developing active TB than females (aIRR = 1.596(95% CI = 1.203-2.117). This was in agreement with the report made by Golub et al. [20].

Concerning IPT initiation time with HAART, among IPT exposed patients; those patients who took IPT with HAART had 84.2% incidence reduction than those who took IPT prior to initiating HAART. This study also noted that there was significant CD4cell count and weight changes after taking IPT-HAART combination therapy compared to cell count at enrollment, which might have contributed for preventing TB recurrence. This finding could serve as a base for further studies to reach an understanding on whether concomitant initiation of IPT with HAART or delayed initiation of IPT is better in terms of efficacy, toxicity or the development of immune reconstitution. In general the current finding encourages further implementation of the therapy in the country so as to decrease the burden of TB among HIV infected patients.

Conclusions

Completion of IPT significantly reduced TB incidence by 96.3% and IPT had significantly protected occurrence of active TB for three years among HIV infected patients. Male sex, CD4 cell count less than 200cells/μl, WHO stage of HIV/AIDS 3 & 4 and being non-employed were risk factors for TB incidence. Concomitant use of HAART with IPT significantly decreased TB incidence by 93.7% more than HAART alone. This result evidenced and supported the WHO recommendations that IPT protected the occurrence of active TB and proved the effectiveness of IPT in reducing TB incidence among HIV infected patients in Ethiopia. Therefore, it should be implemented widely for HIV-infected patients in all parts of the country so as to improve their quality of life by reducing the TB burden and prevent further transmission of TB in the community.

Abbreviations

IPT: 

Isoniazid preventive therapy

aIRR: 

Adjusted incidence rate ratio

HAART: 

Highly active antiretroviral therapy

IR: 

Incidence ratio

PMTCT: 

Prevention of mothers to child transmission of HIV

TB: 

Tuberculosis

WHO: 

World Health Organization

UNAIDS: 

United Nation programs on HIV/AIDS

Declarations

Acknowledgments

Special thanks go to Addis Ababa University, Graduate Study Program and KNCV TB Care I of Ethiopia for financially sponsoring this research.

Funding

Graduate Program of Addis Ababa University and KNCV TB Care I-Ethiopia.

Availability of data and materials

Due to confidentiality issues, the raw data will not be shared.

Authors’ contributions

MS designed the study, supervised the data collection, did the analysis and drafted the manuscript; TGF involved in the design and conduct of the study including approval of the manuscript; GG and DA substantially contributed in data analysis and all authors read and approved the final manuscript.

Competing interests

All authors declared that there is no competing interest.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Ethical approval was obtained from the Research and Ethics Review Committees of the School of Pharmacy, Addis Ababa University, ALERT/AHRI and Addis Ababa Regional Health Bureau. Since the data was taken as part of a routine service, participants’ consent was not a requirement. Instead, Institutional consent was secured from each participating health facility to use the data.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Addis Ababa Health Bureau
(2)
Social and Administrative Pharmacy Working Group, Department of Pharmaceutics and Social Pharmacy, College of Health Sciences, Addis Ababa University
(3)
Aklilu Lemma Institute of Pathobiology, Addis Ababa University
(4)
KNCV TB Care I-Ethiopia

References

  1. Friedland G, Churchyard GJ, Nardell E. Tuberculosis and HIV coinfection: current state of knowledge and research priorities. JID. 2007;196 Suppl 1:S1.View ArticlePubMedGoogle Scholar
  2. WHO. WHO Three I’s Meeting Intensified Case Finding (ICF). Isoniazid Preventive Therapy (IPT) and TB Infection Control (IC) for people living with HIV. Geneva: Report of a Joint World Health Organization HIV/aids and TB Department Meeting; 2008. http://www.who.int/hiv/pub/tb/3is_mreport/en/. (Accessed 20 Oct 2015).Google Scholar
  3. CDC. TB and HIV coinfection. http://www.cdc.gov/hiv/pdf/g-l/cdc-hiv-hivandtb.pdf. (Accessed 4 Oct 2015).
  4. Lawn SD, Harries AD, Anglaret X, et al. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008;22:1897–908.View ArticlePubMedGoogle Scholar
  5. WHO. TB/HIV 2012/2013 factsheet. http://whqlibdoc.who.int/publications/2011/9789241501569_eng.pdf. (Accessed 20 Oct 2015).
  6. FMOH. Health Sector Development Program IV, 2010/11 – 2014/15. Federal Democratic Republic of Ethiopia, Ministry of Health. Version 19. Addis Ababa, Ethiopia.Google Scholar
  7. WHO. Guidelines for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource constrained settings. Geneva, Switzerland; 2011. http://www.who.int/hiv/pub/tb/9789241500708/en/. (Accessed 30 Oct 2015).
  8. World Health Organization Global Tuberculosis Programme/Joint United Nations Programme on HIV/AIDS. Policy statement on preventive therapy against tuberculosis in people living with HIV. Geneva: The Organization; 1998. WHO/TB/98.255. http://www.who.int/docstore/gtb/publications/TB_HIV_polstmnt/index.html. (Accessed on 30 Oct 2015).Google Scholar
  9. WHO. Programmatic update: Antiretroviral Treatment as Prevention (TASP) of HIV and TB. http://www.who.int/hiv/pub/mtct/programmatic_update_tasp/en/. (Accessed 25 Oct 2015).
  10. FMOH: Implementation Guideline for TB/HIV Collaborative Activities in Ethiopia. Federal Ministry of Health: Addis Ababa, Ethiopia; 2008/09.Google Scholar
  11. Belew D. Process evaluation of isoniazid prophylaxis program for HIV positive patients in the ENARP site. Master’s thesis. Addis Ababa: Department of Community Health, Addis Ababa University; 2004.Google Scholar
  12. Vieira de Souza CT, Hökerberg YHM, Pacheco SJB, et al. Effectiveness and safety of isoniazid chemoprophylaxis for HIV-1 infected patients from Rio de Janeiro. Mem Inst Oswaldo Cruz. 2009;104(3):462–7.View ArticleGoogle Scholar
  13. Teferi T, Iyaloo J, Kalibbala M, Makai R, Hango JN, Nkongolo OT, et al. Effect of primary isoniazid preventive therapy on tuberculosis incidence rate among HIV-infected adults enrolled in HIV care in northern Namibia: a retrospective cohort study. In: AIDS 2012 - XIX International AIDS Conference, 2012: Abstract WEPE066. 22-27 July 2012. Washington, D.C. http://pag.aids2012.org/Abstracts.aspx?AID=7130. (Accessed 25 Oct 2015).
  14. Woldehanna S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons (Cochrane Review). The Cochrane Library, Issue 3. Chichester (UK): Wiley; 2004.Google Scholar
  15. Fennera L, Forstera M, Boulleb A, et al. Tuberculosis in HIV programmes in lower-income countries: practices and risk factors. Int J Tuberc Lung Dis. 2011;15(5):620–7.View ArticleGoogle Scholar
  16. Grant AD, Charalambous S, Fielding KL, et al. Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study. JAMA. 2005;293(22):2719–25.View ArticlePubMedGoogle Scholar
  17. Khawcharoenporn T, Apisarnthanarak A, Manosuthi W, et al. Isoniazid preventive therapy and 4-year incidence of pulmonary tuberculosis among HIV infected Thai patients. Int J Tuberc Lung Dis. 2012;16(3):336–41. doi:https://doi.org/10.5588/ijtld.11.0402.View ArticlePubMedGoogle Scholar
  18. World Health Organization (WHO). Report of a “lessons learnt” workshop on the six ProTEST pilot projects in Malawi, South Africa, and Zambia [WHO/HTM/TB/2004.336]. Geneva: WHO; 2004.Google Scholar
  19. Getahun H, Gunneberg C, Granich R, et al. HIV infection associated tuberculosis: the epidemiology and the response. Clinical Infectious Diseases. 2010;50 suppl 3:S201–7. doi:https://doi.org/10.1086/651492.View ArticlePubMedGoogle Scholar
  20. Golub EJ, Pronyk P, Mohapi L, et al. Isoniazid preventive therapy, HAART and tuberculosis Risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009;23(5):631–6.View ArticlePubMedPubMed CentralGoogle Scholar

Copyright

© The Author(s). 2017

Advertisement