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Volume 12, Number 5—May 2006
THEME ISSUE
Tuberculosis Special Section

Research

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

Maria Elvira Balcells*1, Sara L. Thomas*, Peter Godfrey-Faussett*, and Alison D. Grant*Comments to Author 
Author affiliations: *London School of Hygiene and Tropical Medicine, London, United Kingdom

Main Article

Table 3

Studies comparing isoniazid treatment with no treatment in HIV-infected populations*

Author, country, dates Population Intervention/ comparison; blinding Enrolled (n) INH/control Follow up; loss to follow-up; overall or INH vs. control TB cases: culture positive/total (%)
Definition of INH resistance Resistant cases/total tested (% culture positive tested)
Risk for resistant TB/1,000
INH Controls INH Controls INH Controls RR (95% CI)
Randomized controlled trials
Gordin, USA, 1991–1996 (30) Clinic attendees; med. CD4 233/247 6 mo INH 300 mg daily vs. placebo; double blind 260/257 34 mo/33 mo; 6.2% vs. 7% NS/3 NS/6 NS 0/3 (NS) 0/5 (NS) 1.92† 1.94† 0.99 (0.06–6,298.19)
Hawken, Kenya, 1992–1997 (31) Clinic or VCT attendees; med. CD4 321.5/346 6 mo INH 300 mg daily/placebo; double blind 342/342 Med. 1.83 y (range 0–3.41); 32% vs. 27.3% not seen in final 6 m 19/25 (76) 22/23 (95.7) Growth on 0.2 μg/mL INH >1% growth on control medium 2/17 (90) 0/21 (96) 10.05† 1.46† 6.88 (0.01–3,882.85)
Mwinga, Zambia, 1992–1996 (33) VCT attendees 6 mo INH 900 mg twice weekly/placebo; double blind 350/352 Med. 1.8 y; 32.4% vs. 30.3% not seen in final 6 m NS/27 NS/44 NS 0/3 (NS) 1/5 (NS) 1.43† 26.38† 0.05 (0.00–30.47)
Johnson, Uganda, 1993–NS (34) Clinic or counseling attendees 6 mo INH 300 mg daily/placebo; partially double blind‡ 931/787 Mean 2 y/1.6 y (PPD+/anergic); 16.1% vs. 30.6% 36/51 (70.6) 46/64 (71.9) Growth on 0.1 μg/mL INH (BACTEC radiometric method) >1% growth on control medium 5/20 (56) 1/24 (52) 13.69 3.39 4.04 (0.50–32.80)
Rivero, Spain, 1994–2000 (35)
Clinic attendees; med. CD4 193/215
6 mo INH 300 mg daily/no treatment; not blind
82/77
24 mo; 26.8% vs. 7.8%
3/3 (100)
4/4 (100)
NS
3/3 (100)
4/4 (100)
36.59
51.95
0.70 (0.16–3.05)
Cohort study
Moreno, Spain, 1985–1994 (32) Clinic attendees; med. CD4 689/648 9–12 mo INH (dose NS)/no treatment; not blind 29/92 89 mo vs. 60 mo; NS 3/3 (100) 39/43 (90.7) Growth on 0.2 μg/mL INH >1% growth on control medium 2/2 (67) 0/12 (31) 118.64† 5.41† 21.95 (0.04–11,582.31)

*INH, isoniazid; TB, tuberculosis; RR, relative risk; CI, confidence interval; med., median; NS, not stated; Rx, treatment; VCT, voluntary counseling and testing; PPD, purified protein derivative.
†Calculated by adding 0.5 to numerator and denominator of both groups.
‡Unclear whether isoniazid and placebo group received the same number of tablets.

Main Article

1Current affiliation: Department of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

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