Incidence of Tuberculosis among HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy in Europe and North America

Girardi, Enrico; Sabin, Caroline; Monforte, Antonella d’Arminio; Hogg, Bob; Philips, A.; Gill, John; Dabis, François; Reiss, Peter; Kirk, Ole; Bernasconi, Enos; Grabar, Sophie; Justice, Amy C.; Staszewski, Schlomo; Fätkenheuer, Gerd; Sterne, Jonathan A C

doi:10.1086/498315

Cited by 174 publications

(65 citation statements)

References 28 publications

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“…An additional issue is that we do not know the extent of pathogen-specific CD4+ recovery in tissues upon ART, which appears defective for TB in the lungs even after prolonged viral suppression (20). These considerations may account for the persistently greater susceptibility of successfully treated HIV-infected individuals to TB (65). …”

Section: Discussionmentioning

confidence: 99%

Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype

Riou

Tanko

Soares

et al. 2015

The Journal of Immunology

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Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4+ T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4+ T cells specific for common co-pathogens is still unclear. To better understand the dynamics of antigen-specific CD4+ T cells during ART, we assessed the frequency, functional capacity and memory profile of CD4+ T cells specific for Mycobacterium tuberculosis (Mtb) and cytomegalovirus (CMV) in 15 HIV-infected individuals before and one year after ART initiation. After ART initiation, the frequency of Mtb-specific CD4+ T cells showed little change, while CMV-specific CD4+ T cells were significantly lower (p=0.003). There was no difference in the polyfunctional or memory profile of antigen-specific CD4+ T cells before and after ART. The replenishment of antigen-specific CD4+ T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4+ T cells exhibiting a late differentiated profile (CD45RO+CD27−) had a lower capacity to replenish (p=0.019, r=−0.5) compared to cells with an early differentiated profile (CD45RO+CD27+; p=0.04, r=0.45). In conclusion, restoration of co-pathogen-specific memory CD4+ T cells during treated HIV infection is related to their memory phenotype, where early differentiated cells (such as most Mtb-specific cells) have a higher replenishment capacity compared to late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of co-pathogen immunity in HIV-infected individuals on ART.

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Section: Discussionmentioning

confidence: 99%

Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype

Riou

Tanko

Soares

et al. 2015

The Journal of Immunology

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“…Bakeera-Kitaka et al (2011) reported that the most possible risk factor-low baseline CD4 was not found associated with risk of TB which has the same results with our study. CD4 cell count is not proved to be as a sufficient indicator for TB in HIV-infected children (USCDC, 2009) as in adults (Girardi et al, 2005;Lawn et al, 2011;Sterling et al, 2011), less association has been proved in HIVpositive children till now. Besides, the missing values of CD4 count and percentage may limit our analysis.…”

Section: Discussionmentioning

confidence: 99%

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study

Mu¹,

Zhao²,

Sun³

et al. 2014

AIDS Care

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China is a country with high tuberculosis (TB) incidence but relatively low HIV prevalence. However, due to difficulties in diagnosis and reporting, true burden of HIV-associated TB in children is unknown. The objective of this study was to describe the incidence of pulmonary TB (PTB) after antiretroviral therapy (ART) and to study risk factors. A retrospective study was performed based on routinely collected data from China national pediatric free antiretroviral treatment database. A total of 3365 children under 15 years on ART from July 2005 to October 2012 were included. Multivariable logistic regression was used to detect associated factors. Two thousand nine hundred and ninety (89%) children got infected from HIV-positive mother, with median age of 6.7 (4.1, 10.0) years at highly active antiretroviral therapy (HAART) initiation in this program. Seventy-seven (2.3%) children were diagnosed with PTB after ART during 7.3 years cohort observation. Median time of occurrence was 212 (30-514) days. Overall incidence was 0.83 (0.65-1.01)/100 person-years (py), with the peak of 3.6/100 py in the first 3 months after antiretroviral treatment. WHO stage IV at baseline showed 2 (95% CI 1.0-6.8) times more risk for developing TB. Late clinical stage at ART initiation was shown to relate with TB incidence. PTB coinfection leads to higher mortality. Early diagnosis and treatment of HIV are highly required to reduce HIV-associated morbidity and mortality due to TB.

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“…55–59 These time-dependent changes in TB risk reflect the rate of ART-induced immune recovery, as the absolute current CD4 cell count at any given time during ART is a dominant factor associated with TB risk. 60 A 10-fold reduction in TB risk is observed as CD4 cell counts increase from <100 to >500 cells/μl.…”

Section: Impact Of Antiretroviral Therapymentioning

confidence: 99%

Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? [Unresolved issues]

Lawn¹,

Harries²,

Williams³

et al. 2011

int j tuberc lung dis

113

109

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SUMMARY The human immunodeficiency virus (HIV) associated tuberculosis (TB) epidemic remains an enormous challenge to TB control in countries with a high prevalence of HIV. In their 1999 article entitled ‘Will DOTS do it?’, De Cock and Chaisson questioned whether the World Health Organization’s DOTS Strategy could control this epidemic. Data over the past 10 years have clearly shown that DOTS is insufficient as a single TB control intervention in such settings because it does not address the fundamental epidemiological interactions between TB and HIV. Immunodeficiency is a principal river of this epidemic, and the solution must therefore include immune recovery using antiretroviral therapy (ART). Thus, in the era of global ART scale-up, we now ask the question, ‘Will ART do it?’ ART reduces the risk of TB by 67% (95%CI 61–73), halves TB recurrence rates, reduces mortality risk by 64–95% in cohorts and prolongs survival in patients with HIV-associated drug-resistant TB. However, the cumulative lifetime risk of TB in HIV infected individuals is a function of time spent at various CD4-defined levels of risk, both before and during ART. Current initiation of ART at low CD4 cell counts (by which time much HIV-associated TB has already occurred) and low effective coverage greatly undermine the potential impact of ART at a population level. Thus, while ART has proven a critical intervention for case management of HIV-associated TB, much of its preventive potential for TB control is currently being squandered. Much earlier ART initiation with high coverage is required if ART is to substantially influence the incidence of TB.

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Incidence of Tuberculosis among HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy in Europe and North America

Cited by 174 publications

References 28 publications

Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype

Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study

Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? [Unresolved issues]

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