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Heidi M. Soeters, Sonia Napravnik , Monita Patel, Joe Eron , Annelies Van Rie

The effect of tuberculosis treatment on virologic and CD4 cell count response to combination antiretroviral therapy: a systematic review and meta-analysis. Heidi M. Soeters, Sonia Napravnik , Monita Patel, Joe Eron , Annelies Van Rie 44 th Union World Conference – Abstract OP-188-02

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Heidi M. Soeters, Sonia Napravnik , Monita Patel, Joe Eron , Annelies Van Rie

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  1. The effect of tuberculosis treatment on virologic and CD4 cell count response to combination antiretroviral therapy: a systematic review and meta-analysis Heidi M. Soeters, Sonia Napravnik, Monita Patel, Joe Eron, Annelies Van Rie 44th Union World Conference – Abstract OP-188-02 November 2, 2013

  2. Introduction

  3. Introduction • In 2010, the World Health Organization (WHO) recommended that all people living with HIV (PLWH) with TB be initiated on combination antiretroviral therapy (cART), regardless of CD4 count1 • Goal of 100% cART coverage of co-infected patients by 20152 • Many individuals have been and will be initiating cART while concurrently on TB treatment WHO. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2010. WHO and Stop TB Partnership. The Global Plan to Stop TB 2011-2015. 2010.

  4. Introduction • PLWH also on TB treatment may experience a differential response to cART due to: • Drug-drug interactions • Increased risk of drug toxicity • Immune reconstitution inflammatory syndrome (IRIS) • Lower adherence due to high pill burden

  5. Introduction • The effect of TB treatment on a patient’s response to cART has not been fully elucidated and requires careful evaluation • Study aim: Systematic review and meta-analysis of the effect of receiving TB treatment at the time of cART initiation on virologic and CD4 count response among HIV-infected adults

  6. Research Methods

  7. Literature Review • Systematic search of PubMed, EMBASE, and 2009 – 2012 conference abstracts • “HIV AND Tuberculosis AND (Viral Load OR CD4 lymphocyte count OR mortality) AND Antiretroviral therapy” • Citation lists, reviews, & Web of Science citation searches • Human subjects research published since 1997

  8. Study Selection • Eligible studies: • Included antiretroviral-naïve HIV-infected adults initiating cART • Some were receiving TB treatment at cART initiation, some were not receiving TB treatment • Reported virologic and/or CD4 count response to cART • Outcome stratified by TB treatment status • Excluded: studies with children <14 years

  9. Meta-analytic methods • Calculated the method of moments estimate of the between-study variance (τ2) • Used τ2 and random-effects summarization using unconditional variances to calculate relative risks (RRRE) • P-values for standard chi-square homogeneity test statistic were used to assess overall consistency among the effect estimates

  10. Results

  11. Results • 25 eligible cohort studies reported data on 49,578 adults • 8,826 (18%) were receiving TB treatment at cART initiation • 17 virologic response; 21 CD4 count response • Most from sub-Saharan Africa, 9 from Asia, 3 from Europe/North America

  12. Results: Virologic Suppression

  13. Results: Virologic Suppression • Meta-regression • No effect of suppression definition (<50 vs. <400) • No effect of type of cART regimen

  14. Results: Virologic Failure • Virologic failure (7 studies) • Much heterogeneity in outcome measures • HIV RNA levels of >5000 copies/mL • Failed to suppress <400 copies/mL • Rebounded after being previously undetectable or never became undetectable • Time to first value ≥400 • Time to 2 consecutive values ≥5000 copies/mL • Time to first value >500 among those who initially suppressed • Heterogeneity precluded formal meta-analysis

  15. Results: CD4 count response

  16. Conclusions

  17. Conclusions • TB treatment did not increase risk of virologic suppression at 1 to 48 months following cART initiation among adults • Could not make formal meta-analytic conclusions regarding the effect of TB treatment on virologic failure or CD4 count response, but review of the literature suggests: • TB treatment does not appear to affect virologic rebound • TB treatment is associated with lower CD4 counts at cART initiation and during follow-up, but comparable increase in CD4 count • Standardization of reported outcomes is needed to facilitate future between-study comparisons • Studies reporting cART regimen-specific estimates would further improve our knowledge

  18. Acknowledgements • Mellanye Lackey • Harry Moultrie • Alan Brookhart

  19. Thank you!Questions?

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