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.
Quality assessed with a modified Newcastle-Ottawa scale for cohorts with A/B/C according to all/some/few criteria met in each domain.
Mean.
Inter-quartile range.
5 mm cut-off used in tuberculin skin test.
Cut-off used in tuberculin skin test not stated.
Reference value.
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