The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study

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Abstract

Background

Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan.

Methods

A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test.

Results

There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06–0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16–30 days and at 31–60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01).

Conclusion

The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31–60 days of TB treatment might be optimal after considering the risks and benefits.

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Most cited references 28

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Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa.

Stephen D Lawn, Landon Myer, Linda-Gail Bekker … (2007)

To determine the burden and impact of immune reconstitution disease (IRD) associated with tuberculosis (TB) among patients initiating antiretroviral treatment (ART) in sub-Saharan Africa. Retrospective analysis of a study cohort enrolled over 3 years within a community-based ART service in South Africa. Patients receiving treatment for TB at the time ART was initiated (n = 160) were studied. Cases of TB-associated IRD during the first 4 months of ART were ascertained. The median baseline CD4 cell count was 68 cells/microl [interquartile range (IQR), 29-133 cells/microl) and ART was initiated after a median of 105 days (IQR, 61-164 days) from TB diagnosis. Although IRD was diagnosed in just 12% (n = 19) of patients overall, IRD developed in 32% (n = 12) of those who started ART within 2 months of TB diagnosis. Pulmonary involvement was observed in 84% (n = 16) and intra-abdominal manifestations were also common (37%). Overall, 4% (n = 7) of the cohort required secondary level health-care for IRD and two (1%) patients died. In multivariate analysis, risk of IRD was strongly associated with early ART initiation and low baseline CD4 cell count. Of patients with CD4 counts 120 days of TB diagnosis were 100%, 33%, 14%, 7% and 0%, respectively. The risk of TB-associated IRD in this setting is very high for those with low baseline CD4 cell counts initiating ART early in the course of antituberculosis treatment. However, most cases were self-limiting; overall secondary health-care utilization and mortality risk from IRD were low.

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Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy.

F. Lampe, M. Johnson, Keertan Dheda … (2004)

The benefit of highly active antiretroviral therapy (HAART) in the treatment of patients coinfected with tuberculosis (TB) and human immunodeficiency virus (HIV) is unclear because of concerns about treatment-related complications. We compared outcomes in patients starting TB treatment during the pre-HAART era (before 1996; n=36) with those in patients starting treatment during the HAART era (during or after 1996; n=60). During a median of 3.6 years of follow-up, 49 patients died or had an AIDS event. Compared with patients in the pre-HAART group, those in the HAART group had a lower risk of death (cumulative at 4 years, 43% vs. 22%; P=.012) and of death or having an AIDS event (69% vs. 43%; P=.023). Event risk within the first 2 months of TB treatment was exceptionally high in patients with CD4(+) cell counts <100 cells/mm(3) and declined thereafter. HAART use during follow-up was associated with a marked reduction in event risk (adjusted hazard ratio, 0.38 [95% confidence interval, 0.16-0.91]). HAART substantially reduces new AIDS events and death in coinfected patients. Those with a CD4(+) cell count <100 cells/mm(3) have a high event risk during the intensive phase of anti-TB treatment. These data should be taken into account when deciding to delay HAART in coinfected patients with CD4(+) cell counts <100 cells/mm(3).

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Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection.

L Swaden, Richard Miller, Krista Schwenk … (2006)

Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co-infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti-TB treatment in the era of effective antiretroviral therapy. The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co-infected with HIV. 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti-TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co-infected patients (p<0.001; p = 0.006), although all cause interruption of anti-TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re-treatment. Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti-TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals.

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Author and article information

Contributors

Chin-Hui Yang

Kuan-Jung Chen

Jih-Jin Tsai

Yu-Hui Lin

Shu-Hsing Cheng

Kwei-Feng Wang

Hung-Yi Chiou

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central

ISSN (Electronic): 1471-2334

Publication date Collection: 2014

Publication date (Electronic): 4 June 2014

Volume: 14

Page: 304

Affiliations

[1 ]Centers for Disease Control, Ministry of Health and Welfare, 5F, No.6, Linsen S. Rd., Taipei City 100, Taiwan

[2 ]Ph. D. program in School of Public Health, Taipei Medical University, No. 250, 469 Wu-Hsing Street, Taipei, Taiwan

[3 ]Department of Chest Medicine, RenAi branch of Taipei City Hospital, No. 10, Section 4, Ran-Ai Road, Taipei, Taiwan

[4 ]School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Kaohsiung, Taiwan

[5 ]Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, , No.100, Tzyou 1st Road, Kaohsiung, Taiwan

[6 ]Tropical Medicine Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Tzyou 1st Road, Kaohsiung, Taiwan

[7 ]Section of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, No.1650, Sec. 4, Taiwan Boulevard, Taichung, Taiwan

[8 ]Section of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, No. 1492, Chung-Shan Road, Taoyuan, Taiwan

[9 ]School of Public Health, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, Taiwan

Article

Publisher ID: 1471-2334-14-304

DOI: 10.1186/1471-2334-14-304

PMC ID: 4058447

PubMed ID: 24897928

SO-VID: 06738128-4719-46b5-859d-d4fd332ab9f7

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study

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Abstract

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Conclusion

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Point-of-Care Testing for Infectious Diseases Super Collection

Most cited references 28

Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa.

Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy.

Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection.

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