Author
Listed:
- Amitabh B Suthar
- Stephen D Lawn
- Julia del Amo
- Haileyesus Getahun
- Christopher Dye
- Delphine Sculier
- Timothy R Sterling
- Richard E Chaisson
- Brian G Williams
- Anthony D Harries
- Reuben M Granich
Abstract
In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection. Background: Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings: PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. : Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions: Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic. Review Registration: International Prospective Register of Systematic Reviews CRD42011001209 Background: Tuberculosis—a contagious bacterial infection— is a global public-health problem. In 2010, 8.8 million people developed active tuberculosis and 1.4 million people died from the disease. Tuberculosis can be cured by taking powerful antibiotics regularly for several months, and between 1995 and 2010, 46 million people with tuberculosis were successfully treated using DOTS—a directly observed antibiotic regimen designed by the World Health Organization (WHO). Now, though, the HIV epidemic is compromising global tuberculosis control efforts. HIV-positive people are very susceptible to tuberculosis because HIV, the virus that causes AIDS, destroys the immune system cells (including CD4 lymphocytes) that normally combat tuberculosis. In 2010, 1.1 million of the new (incident) cases of tuberculosis were among the 34 million people living with HIV, and 350,000 people died of HIV-associated tuberculosis, making tuberculosis the leading cause of death among HIV-positive people. To tackle HIV-associated tuberculosis, which occurs mainly in developing countries, WHO now recommends that HIV and tuberculosis programs use collaborative approaches such as the Three I's for HIV/TB strategy—intensified tuberculosis case-finding among HIV-positive people, isoniazid preventative therapy for HIV-positive people without active tuberculosis, and (tuberculosis) infection control in healthcare facilities, social settings, and households. Why Was This Study Done?: Despite progress in scaling up the Three I's for HIV/TB strategy, complementary interventions are still needed to prevent tuberculosis in HIV-positive people. Antiretroviral therapy (ART) lowers the viral load of people infected with HIV and restores their immune system function and could, therefore, prevent HIVassociated tuberculosis, in addition to treating HIV infection. WHO recommends ART for all HIV-positive adults with a CD4 count of less than 350 cells/μl of blood and for all HIVpositive, tuberculosis-positive individuals irrespective of their CD4 count. However, the evidence for ART's preventative impact on tuberculosis has not been systematically examined. Here, the researchers undertake a systematic review (a search that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical method for combining the results of studies) to investigate the impact of ART initiated at various CD4 counts on the development of tuberculosis in HIV-positive adults in developing countries. What Did the Researchers Do and Find?: The researchers found 11 studies that compared tuberculosis incidence by ART status in HIV-infected adults over periods longer than six months on average in developing countries and undertook meta-analyses of these studies based on four categories of CD4 count at ART initiation (less than 200 cells/μl, 200–350 cells/μl, greater than 350 cells/μl, and any CD4 count). For all these categories, ART was strongly associated with a reduction in the incidence of tuberculosis. For example, the meta-analysis of the two studies that reported on participants in whom ART was initiated at a CD4 count less than 200 cells/μl yielded a hazard ratio (HR) of 0.16. That is, study participants starting ART when their CD4 count was below 200 cells/μl were about one-sixth as likely to develop tuberculosis as participants not receiving ART. In the metaanalysis of all 11 studies, study participants receiving ART were about one-third as likely to develop tuberculosis as study participants receiving no ART, irrespective of their CD4 count (HR 0.35). Importantly, the CD4 count at which ART was initiated did not significantly alter the magnitude of ART's preventive effect on tuberculosis development. What Do These Findings Mean?: These findings suggest that ART is strongly associated with a reduction in the incidence of tuberculosis in HIV-positive adults in developing countries, whatever the CD4 count at ART initiation. Because most of the studies in this meta-analysis were observational, these results do not show that ART causes a reduction in tuberculosis incidence—other unknown factors shared by the study participants who received ART may be responsible for their lower tuberculosis incidence. Moreover, factors such as variations in diagnostic methods among the studies included in this meta-analysis may have affected the accuracy of these findings. Nevertheless, the key finding that ART is associated with a significant reduction in tuberculosis cases among adults with CD4 counts greater than 350 cells//μl should be considered by healthcare providers, policymakers, and people living with HIV when weighing the benefits and risks of early ART initiation. It also suggests that early ART initiation (in combination with expanded HIV testing) could be a key component of future global and national strategies to control HIV-associated tuberculosis. Additional Information: Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001270.
Suggested Citation
Amitabh B Suthar & Stephen D Lawn & Julia del Amo & Haileyesus Getahun & Christopher Dye & Delphine Sculier & Timothy R Sterling & Richard E Chaisson & Brian G Williams & Anthony D Harries & Reuben M , 2012.
"Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis,"
PLOS Medicine, Public Library of Science, vol. 9(7), pages 1-15, July.
Handle:
RePEc:plo:pmed00:1001270
DOI: 10.1371/journal.pmed.1001270
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Cited by:
- Anna Odone & Silvia Amadasi & Richard G White & Theodore Cohen & Alison D Grant & Rein M G J Houben, 2014.
"The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis,"
PLOS ONE, Public Library of Science, vol. 9(11), pages 1-12, November.
- Dimie Ogoina & Finomo Finomo & Tubonye Harry & Otonyo Inatimi & Ikenna Ebuenyi & Wolo-wolo Tariladei & Abimbola Anne Afolayan, 2015.
"Factors Associated with Timing of Initiation of Antiretroviral Therapy among HIV-1 Infected Adults in the Niger Delta Region of Nigeria,"
PLOS ONE, Public Library of Science, vol. 10(5), pages 1-12, May.
- Jockers, Dominik & Langlotz, Sarah & French, Declan & Bärnighausen, Till, 2021.
"HIV treatment and worker absenteeism: Quasi-experimental evidence from a large-scale health program in South Africa,"
Journal of Health Economics, Elsevier, vol. 79(C).
- Andrew D Kerkhoff & Katharina Kranzer & Taraz Samandari & Jessica Nakiyingi-Miiro & Christopher C Whalen & Anthony D Harries & Stephen D Lawn, 2012.
"Systematic Review of TST Responses in People Living with HIV in Under-Resourced Settings: Implications for Isoniazid Preventive Therapy,"
PLOS ONE, Public Library of Science, vol. 7(11), pages 1-12, November.
- Tendesayi Kufa & Tonderai Mabuto & Evans Muchiri & Salome Charalambous & Dominique Rosillon & Gavin Churchyard & Rebecca C Harris, 2014.
"Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis,"
PLOS ONE, Public Library of Science, vol. 9(11), pages 1-11, November.
- Dilbar Sadirova & Ruzanna Grigoryan & Nargiza Parpieva & Venera Barotova & Aleksandr Trubnikov & Lola Kalandarova & Jamshid Gadoev & Davron Mukhtarov & Mariana Buziashvili & Nestani Tukvadze & Arax Ho, 2021.
"Incidence Rate and Risk Factors for Tuberculosis among People Living with HIV: A 2015–2017 Cohort from Tashkent, Uzbekistan,"
IJERPH, MDPI, vol. 18(11), pages 1-10, May.
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