Article

Risk Factors for Active Tuberculosis after Antiretroviral Treatment Initiation in Abidjan

INSERM U593, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 08/2005; 172(1):123-7. DOI: 10.1164/rccm.200410-1342OC
Source: PubMed

ABSTRACT In sub-Saharan Africa: (1) tuberculosis is the first cause of HIV-related mortality; (2) the incidence of tuberculosis in adults receiving highly active antiretroviral therapy (HAART) is lower than in untreated HIV-infected adults but higher than in HIV-negative adults; and (3) factors associated with the occurrence of tuberculosis in patients receiving HAART have never been described.
To look for the risk factors for active tuberculosis in HIV-infected adults receiving HAART in Abidjan.
Seven-year prospective cohort of HIV-infected adults, with standardized procedures for documenting morbidity. We analyzed the incidence of active tuberculosis in patients who started HAART and the association between the occurrence of tuberculosis and the characteristics of these patients at HAART initiation.
A total of 129 adults (median baseline CD4 count 125/mm(3)) started HAART and were then followed for 270 person-years (P-Y). At HAART initiation, 31 had a history of tuberculosis and none had current active tuberculosis. During follow-up, the incidence of active tuberculosis was 4.8/100 P-Y (95% confidence interval [CI], 2.5-8.3) overall, 3.0/100 P-Y (95% CI, 1.1-6.6) in patients with no tuberculosis history, and 11.3/100 P-Y (95% CI, 4.1-24.5) in patients with a history of tuberculosis (adjusted hazard ratio, 4.64; 95% CI, 1.29-16.62, p = 0.02).
The risk of tuberculosis after HAART initiation was significantly higher in patients with a history of tuberculosis than in those with no tuberculosis history. If confirmed by others, this finding could lead to assessment of new patterns of time-limited tuberculosis secondary chemoprophylaxis during the period of initiation of HAART in sub-Saharan African adults.

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    • "Greater hazards of tuberculosis among those with the highest ML ratios could potentially have been explained by known risk factors for tuberculosis in this population [24, 26] which include a CD4+ T-cell of <100 cells/µL, WHO stage 3 or 4 HIV infection or disease, male sex, and/or a past history of tuberculosis. To address these potential confounders, these covariates were included in the Cox proportional hazards model (Table 2). "
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    ABSTRACT: Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis.
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