BACKGROUND: The human immunodeficiency virus (HIV) alters the presentation of pulmonary tuberculosis (PTB), but it remains unclear whether alterations occur at a CD4 cell threshold or throughout HIV ...infection.OBJECTIVE: To better understand the relationship between CD4 count and
clinical and radiographic presentation of PTB.SETTING AND DESIGN: Initial presentations of culture-confirmed PTB patients evaluated at a Ugandan national TB referral center and an affiliated research unit were compared by HIV status and across 11 CD4 cell count strata: 0-50 to >500
cells/μl.RESULTS: A total of 873 HIV-infected PTB cases were identified. Among HIV-infected PTB cases with CD4 < 50, 21% had a normal chest X-ray (CXR) vs. 2% with CD4 > 500, with a continuous trend across CD4 strata (test for trend, P < 0.001). All radiographic manifestations
of PTB displayed significant trends across CD4 strata. HIV-infected vs. non-HIV-infected patients had no significant difference in CXR findings of miliary patterns or pleural effusion at CD4 > 100, normal CXR or fibrosis at CD4 > 150, adenopathy at CD4 > 250, and cavitation or upper
lung disease at CD4 > 300. Twenty-three per cent of co-infected cases with CD4 < 50 and 1% with CD4 > 500 had negative acid-fast bacilli (AFB) smears, with a significant trend between (P < 0.001).CONCLUSION: Variations in CXR appearance and AFB smear correlate with CD4
decline in significant, continuous trends.
BackgroundHuman immunodeficiency virus (HIV)–infected patients with tuberculosis (TB) respond to effective antituberculous therapy, but their prognosis remains poor. Mounting evidence from clinical ...studies supports the concept of copathogenesis in which immune activation that is triggered by TB and mediated by cytokines stimulates viral replication and worsens HIV infection, especially when immune function is preserved MethodsWe performed a phase 2, randomized, double-blind, placebo-controlled clinical trial in Kampala, Uganda, to determine whether immunoadjuvant prednisolone therapy in HIV-infected patients with TB who have CD4+ T cell counts ⩾200 cells/μL is safe and effective at increasing CD4+ T cell counts ResultsShort-term prednisolone therapy reduced levels of immune activation and tended to produce higher CD4+ T cell counts. Although prednisolone therapy was associated with a more rapid clearance of Mycobacterium tuberculosis from the sputum, it was also associated with a transient increase in HIV RNA levels, which receded when prednisolone therapy was discontinued. The intervention worsened underlying hypertension and caused fluid retention and hyperglycemia ConclusionThe benefits of prednisolone therapy on immune activation and CD4+ T cell counts do not outweigh the risks of adverse events in HIV-infected patients with TB and preserved immune function
Tuberculosis remains a serious threat to public health, especially in sub-Saharan Africa. To determine the host and environmental factors responsible for tuberculosis in African households, the ...authors performed a prospective cohort study of 1,206 household contacts of 302 index cases with tuberculosis enrolled in Uganda between 1995 and 1999. All contacts were systematically evaluated for active tuberculosis and risk factors for active disease. Among the 1,206 household contacts, 76 secondary cases (6%) of tuberculosis were identified. Of these cases, 51 were identified in the baseline evaluation, and 25 developed during follow-up. Compared with index cases, secondary cases presented more often with minimal disease. The risk for secondary tuberculosis was greater among young children than adults (10% vs. 1.9%) and among human immunodeficiency virus-seropositive than -seronegative contacts (23% vs. 3.3%). Host risk factors could not be completely separated from the effects of environmental risk factors, suggesting that a household may represent a complex system of interacting risks for tuberculosis.
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.
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.
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.
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.
Infection with
Mycobacterium tuberculosis
is the most common human infection worldwide. As the epidemic of human immunodeficiency virus (HIV) infection continues to evolve, the risk of dual infection ...with HIV and
M. tuberculosis
may be substantial in young adults, especially in developing countries.
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HIV infection confers the greatest known risk for the development of tuberculosis, both for the reactivation of latent infection and for progressive primary disease.
2
–
5
Moreover, once active tuberculosis develops in HIV-infected persons, mortality is high, despite good clinical and microbiologic responses to antituberculous therapy.
6
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11
Preventive therapy has been proposed as a strategy to control tuberculosis . . .
Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human immunodeficiency virus (HIV)–coinfected (HIV/TB) ...patients and patients infected with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluated. T cells were expanded at the site of MTB infection, irrespective of HIV status. Apoptosis of CD4 and non-CD4 T cells in the pleural space occurred in both HIV/TB and TB. Interferon (IFN)–γ levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-γ–producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor–α, Fas-ligand, and Fas, were increased in pleural fluid, compared with plasma. These data suggest that continued exposure of immunoreactive cells to MTB at sites of infection may initiate a vicious cycle in which immune activation and loss of antigen-responsive T cells occur concomitantly, thus favoring persistence of MTB infection
OBJECTIVE: To test the feasibility of measuring household ventilation and evaluate whether ventilation is associated with tuberculosis (TB) in household contacts in Kampala, Uganda.DESIGN: Adults ...with pulmonary TB and their household contacts received home visits to ascertain social
and structural household characteristics. Ventilation was measured in air changes per hour (ACH) in each room by raising carbon dioxide (CO2) levels using dry ice, removing the dry ice, and measuring changes in the natural log of CO2 (lnCO2) over time. Ventilation
was compared in homes with and without co-prevalent TB.RESULTS: Members of 61 of 66 (92%) households approached were enrolled. Households averaged 5.4 residents/home, with a median of one room/home. Twelve homes (20%) reported co-prevalent TB in household contacts. Median ventilation for
all rooms was 14 ACH (interquartile range IQR 10-18). Median ventilation was 12 vs. 15 ACH in index cases' sleeping rooms in households with vs. those without co-prevalent TB (P = 0.12). Among smear-positive indexes not infected by the human immunodeficiency virus (HIV), median
ventilation was 11 vs. 17 ACH in index cases' sleeping rooms in homes with vs. those without co-prevalent TB (P = 0.1).CONCLUSION: Our findings provide evidence that a simple CO2 decay method used to measure ventilation in clinical settings can be adapted to homes, adding
a novel tool and a neglected variable, ventilation, to the study of household TB transmission.
Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4⁺ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis ...may block effects of immune activation on T cells and slow HIV disease progression.
We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/μL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4⁺ T-cell counts of < 250 cells/μL, AIDS, or death.
Intervention and comparison arms had similar median CD4⁺ counts (517 and 534 cells/μL, respectively) and HIV RNA levels (4.6 and 4.7 log₁₀ copies/μL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis.
Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4⁺T-cell counts of >350 cells/μL was safe and associated with clinical benefits.
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