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. 2017 Dec 14;5:e4165. doi: 10.7717/peerj.4165

Table 1. Summary of studies.

First author, year Country Years of study Study description Study conclusion Number in cohortg Ethnicity CD4 count category Number of TB cases Patient years TB incidence per 1,000 person-years Bacteriologicaly confirmed TB (%) TST positive (%) Age range (median) Male (%) Epidemic type Qualitya (selection/ comparability/outcome)
Assebe, 2015 Ethiopia 2008–2012 Retrospective cohort study of patients in pre-ART care at a tertiary hospital focusing on the effect of IPT. Cohort comprised IPT (n = 294) and non-IPT (n = 294) patients sampled from 3,476 in pre-ART care. Median follow-up 24.1 months. Adjusted hazard ratio from Cox PH model reported for CD4 categories (adjusting for IPT use) based on n = 585 patients. IPT found to halve TB incidence. 588 Black African <350 49 1297.5 aHR= 3.16 (1.04–3.92) 15–64 38 Heterosexual B/A/B
350–499 aHR = 2.87 (1.37–6.03)
≥500 aHR = 1g
Collins, 2015 Haiti 2005–2012 Open-label RCT, using the CIPRA-HT001 cohort to receive early ART (n = 408) or delayed ART (i.e., when CD4 < 200; n = 408). Median follow-up of 4.4 in the early treatment arm and a median 3.9 years in the delayed treatment arm. 43 participants with prevalent TB at initiation excluded from incidence analysis, which reported an adjusted HR of TB incidence per 50 cells/mm3 CD4 decrement from Cox PH models (this included person-time on ART). Model including adjustments for treatment group and PPD-status/IPT used. Delayed ART initiation results in persistent increased TB risk. 816 96 aHR = 1.24 (1.11–1.38) per 50 CD4 cells/mm3 decline 61 27e ≥18 (40) 42 B/A/A
Grant, 2009 UK 1996–2005 An observational cohort study of patients (UK Collaborative HIV Cohort, restricted to those who joined prior to 2006); median follow-up 4.2 years. TB within 3 months of enrolment excluded, as were individuals without CD4 count or who were lost to follow-up or died within 3 months of first visit. TB incidence reported separated for those not taking ART. Early HIV diagnosis and IPT key to reducing the particularly high TB incidence in non-white & low-CD4 PLHIV in the UK. 22,833 Black African <50 9 176 51.1 ≥16 (34) 36 Heterosexual A/B/B
50–199 13 612 21.2
200–349 14 1,453 9.6
350–500 7 1,443 4.9
>500 7 1,553 4.5
White <50 9 850 10.6 ≥16 (35) 92 MSM
50–199 25 2,631 9.5
200–349 20 6,636 3
350–500 9 7,548 1.2
>500 3 9,560 0.3
Other <50 3 252 11.9 ≥16 (34) 77 MSM
50–199 4 535 7.5
200–349 5 1,422 3.5
350–500 11 1,587 6.9
>500 1 2,180 0.5
Markowitz, 1997 USA 1988–1990 Prospective, multi-center cohort study of HIV seropositive patients (the Pulmonary Complications of HIV Infection Study) representative of US PLHIV; median follow-up of 53 months. Around 4% of patients were taking IPT. TB incidence increased with PPD induration. TB incidence highest in patients with CD4 <200 and PPD patients. 1,130 White/Black /Hispanic <200 17 1,417 12 71 6d 18–67 (37b) 87 MSM/IDU /heterosexual C/B/A
≥200 14 2,800 5
Monge, 2014 Spain 2004–2010 Open, multi-center, prospective cohort of ART naïve patients (CoRIS = Spanish AIDS Research Network Cohort). Around half of TB cases were in people on ART. Adjusted rate ratios by CD4 category from Poisson regression (adjusting for ART-status) were therefore used. TB episodes during follow-up and up to 3 months prior to enrolment were included. Early HIV diagnosis and ART should be used to help address high TB incidence in PLHIV. 6,811 <200 124 aHR = 5.20(3.25–8.33) 65 >13 80 Heterosexual /IDU B/A/C
200–350 32 aHR = 1.54(1.01–2.34)
>350 37 aHR = 1g
Nicholas, 2011 Guinea, Kenya, Malawi, Mozambique, Nigeria & Uganda 2006–2008 Multi-center, retrospective cohort study based on the FUCHIA database from all sub-Saharan Médicins sans Frontières HIV programmes. TB at, or within 15 days of, enrolment excluded; patients with <15 days of follow-up excluded. Median follow-up 9 months. TB recorded pre-ART and during ART. Median pre-ART follow-up of 9 months. Importance of early HIV diagnosis and treatment and implementation of the 3Is. 8,998 Black African <50 59 98 602 27–40c (33) 27 Heterosexual A/A/B
50–99 68 170 401
100–199 162 732 221
≥200 398 6,180 64
Wolday, 2003 Ethiopia 1997–2001 A prospective cohort study (Ethio-Netherlands AIDS Research Project = ENARP) to study biomarkers associated with TB progression. HIV-positive and negative factory workers with an overall median follow-up of 3.8 years and 6-monthly assessments. Low CD4 and high viral load associated with TB incidence; successful TB treatment does not reduce viral load. 95 Black African <200 5 46 107.6 50 38d (34) 52 Heterosexual C/A/B
200–499 5 121 41.2
≥500 0 43 0

Notes.

a

Quality assessed with a modified Newcastle-Ottawa scale for cohorts with A/B/C according to all/some/few criteria met in each domain.

b

Mean.

c

Inter-quartile range.

d

5 mm cut-off used in tuberculin skin test.

e

Cut-off used in tuberculin skin test not stated.

f

Reference value.

g

Cohort number restricted to those included in TB incidence calculation.

aHR
adjusted hazard ratio
ART
antiretroviral therapy
IPT
isoniazid preventive therapy
TB
tuberculosis
RCT
randomized controlled trial
PPD
purified protein derivative
TST
tuberculin skin test
PLHIV
people living with HIV
IDU
injecting drug users
MSM
men who have sex with men