BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.
BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infectedpersons.
Authors: J Del Amo; A Petruckevitch; A N Phillips; A M Johnson; J M Stephenson; N Desmond; T Hanscheid; N Low; A Newell; A Obasi; K Paine; A Pym; C M Theodore; K M De Cock Journal: AIDS Date: 1996-11 Impact factor: 4.177
Authors: C L Daley; P M Small; G F Schecter; G K Schoolnik; R A McAdam; W R Jacobs; P C Hopewell Journal: N Engl J Med Date: 1992-01-23 Impact factor: 91.245
Authors: R S Wallis; M Vjecha; M Amir-Tahmasseb; A Okwera; F Byekwaso; S Nyole; S Kabengera; R D Mugerwa; J J Ellner Journal: J Infect Dis Date: 1993-01 Impact factor: 5.226
Authors: G Poli; A Kinter; J S Justement; J H Kehrl; P Bressler; S Stanley; A S Fauci Journal: Proc Natl Acad Sci U S A Date: 1990-01 Impact factor: 11.205
Authors: P Nunn; R Brindle; L Carpenter; J Odhiambo; K Wasunna; R Newnham; W Githui; S Gathua; M Omwega; K McAdam Journal: Am Rev Respir Dis Date: 1992-10
Authors: Vasan K Sambandamurthy; Steven C Derrick; Kripa V Jalapathy; Bing Chen; Robert G Russell; Sheldon L Morris; William R Jacobs Journal: Infect Immun Date: 2005-02 Impact factor: 3.441
Authors: Harriet Mayanja-Kizza; Edward Jones-Lopez; Alphonse Okwera; Robert S Wallis; Jerrold J Ellner; Roy D Mugerwa; Christopher C Whalen Journal: J Infect Dis Date: 2005-02-08 Impact factor: 5.226
Authors: David H Canaday; Mianda Wu; Shigou Lu; Htin Aung; Pierre Peters; Joy Baseke; Wilma Mackay; Harriet Mayanja-Kizza; Zahra Toossi Journal: AIDS Res Hum Retroviruses Date: 2009-02 Impact factor: 2.205
Authors: Macarthur Charles; Francine Noel; Paul Leger; Patrice Severe; Cynthia Riviere; Carole Anne Beauharnais; Erica Miller; John Rutledge; Heejung Bang; Wesley Shealey; Richard T D'Aquila; Roy M Gulick; Warren D Johnson; Peter F Wright; Jean William Pape; Daniel W Fitzgerald Journal: Bull World Health Organ Date: 2008-12 Impact factor: 9.408
Authors: Conrad Kabali; Lillian Mtei; Daniel R Brooks; Richard Waddell; Muhammad Bakari; Mecky Matee; Robert D Arbeit; Kisali Pallangyo; C Fordham von Reyn; C Robert Horsburgh Journal: Tuberculosis (Edinb) Date: 2013-03-22 Impact factor: 3.131