Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Kufa, Tendesayi; Mabuto, Tonderai; Muchiri, Evans; Charalambous, Salome; Rosillon, Dominique; Churchyard, Gavin J.; Harris, Rebecca

doi:10.1371/journal.pone.0111209

Cited by 36 publications

(36 citation statements)

References 45 publications

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“…TB in HIV infection depends on the person's immune status (host), on the virulence of the virus (agent) and on external factors such as reinfections 8,9 . The incidence is lower than that reported in a systematic review summarizing findings from 32 cohorts of HIV-infected patients from high and intermediate tuberculosis burden settings taking ART 1 . A study in Ifakara, another rural area in Tanzania reported the TB incidence among HIV-infected persons to be 3.4/100 PY 2 .…”

Section: Discussioncontrasting

confidence: 55%

“…A systematic review was done on TB incidence among HIV infected persons on ART 1 , but only very few studies have been done on TB incidence among ART naïve HIV-infected persons with medium/high CD4 count not on ART [2][3][4] . The lowest and highest incidences in these studies were 2.7 and 10.5 per 100 person years (PY), respectively, both reported from South Africa 3,4 .…”

Section: Introductionmentioning

confidence: 99%

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Tuberculosis among HIV-infected population: incidence and risk factors in rural Tanzania

Said¹,

Verver²,

Kalingonji

et al. 2017

Afr H. Sci.

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Background: The incidence of tuberculosis among HIV-infected populations with high CD4 count in high burden countries has not been well studied. Objective: To assess the TB incidence in HIV-infected adults and its associated risk factors. Method: A cohort study with retrospective review of medical records and prospective follow-up of HIV-infected adult participants attending CTC who were 18-55 years old, had CD4 count more than 250 cells/mm 3 in the period of 2008-2010 and were not on ART at enrolment. Cox proportional hazard regression was used to explore the predictors of incident TB. Results: Overall 777 (24%) of 3,279 CTC enrolled HIV-infected adults fulfilled the inclusion criteria of the study. The incidence of TB in the study population ranged from 0.8/100 per person years (PY) at risk (95% CI 0.5-1.3) in the main analysis to 1.7/100 PY at risk (95% CI 1.0-2.6) in sensitivity analyses. Only prior history of TB disease was found to have a significant association with an increased risk of TB, hazard ratio 5.7 (95% CI 2.0-16.4, p value 0.001). Conclusion: Tuberculosis incidence among HIV-infected adults with medium/high CD4 count in Bagamoyo is lower than in other high TB burden countries. Previously TB treated patients have a much higher risk of getting TB again than those who never had TB before.

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Section: Discussioncontrasting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Tuberculosis among HIV-infected population: incidence and risk factors in rural Tanzania

Said¹,

Verver²,

Kalingonji

et al. 2017

Afr H. Sci.

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“…Early ART provides public health benefits by way of a reduced risk of transmission;23, 24 in this study we show individual-level health benefits in addition to those presented in the START primary publication. Our findings could be of particular importance in regions where a high burden of bacterial diseases might exacerbate the natural history of HIV disease 25, 26, 27, 28, 29, 30, 31…”

Section: Discussionmentioning

confidence: 79%

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

et al. 2017

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SummaryBackgroundThe effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.MethodsThe START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048.FindingsPatients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26–0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71–0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50–1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately.InterpretationImmediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count.FundingNational Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

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“…On the one hand, tuberculosis and bacterial diseases are common diseases that act as opportunistic infections in people living with HIV, and we suspect that there is no higher CD4+ threshold that could identify a sharp decrease in risk. [39][40][41][42] On the other hand, patients with slow progression of HIV infection, who represent a small minority of patients, may not have the same benefitrisk ratio from earlier ART as other patients.…”

Section: Discussionmentioning

confidence: 99%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,021

447

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BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

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Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Cited by 36 publications

References 45 publications

Tuberculosis among HIV-infected population: incidence and risk factors in rural Tanzania

Tuberculosis among HIV-infected population: incidence and risk factors in rural Tanzania

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

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