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Opportunistic diseases diminish the clinical benefit of immediate antiretroviral therapy in HIVtuberculosis co-infected adults with low CD4+ cell counts

Worodria, Williama,b,c; Ssempijja, Victord; Hanrahan, Coleene; Ssegonja, Richardf; Muhofwa, Abdallaha; Mazapkwe, Doreena; Mayanja-Kizza, Harrieta,c; Reynolds, Steven J.b,e,g; Colebunders, Roberth; Manabe, Yukari C.a,b

doi: 10.1097/QAD.0000000000001941

Introduction: HIVtuberculosis (TB) co-infection remains an important cause of mortality in sub-Saharan Africa. Clinical trials have reported early (within 2 weeks of TB therapy) antiretroviral therapy (ART) reduces mortality among HIV–TB co-infected research participants with low CD4+ cell counts, but this has not been consistently observed. We aimed to evaluate the current WHO recommendations for ART in HIV–TB co-infected patients on mortality in routine clinical settings.

Methods: We compared two cohorts before (2008–2010) and after (2012–2013) policy change on ART timing after TB and examined the effectiveness of early versus delayed ART on mortality in HIV–TB co-infected participants with CD4+ cell count 100 cells/μl or less. We used inverse probability censoring-weighted Cox models on baseline characteristics to balance the study arms and generated hazard ratios for mortality.

Results: Of 356 participants with CD4+ cell counts 100 cells/μl or less, 180 were in the delayed ART cohorts whereas 176 were in the early ART cohorts. Their median age (32.5 versus 32 years) and baseline CD4+ cell counts (26.5 versus 26 cells/μl) respectively were similar. There was no difference in mortality rates of both cohorts. The risk of death increased in participants with a positive Cryptococcal antigen (CrAg) test in both the early ART cohort (aHR = 2.6, 95% CI 1.0–6.8; P = 0.045) and the delayed ART cohort (aHR = 4.2, 95% CI 1.9–9.0; P < 0.001

Conclusion: Early ART in patients with HIV–TB co-infection was not associated with reduced risk of mortality in routine care. Asymptomatic Cryptococcal antigenaemia increased the risk of mortality in both cohorts.

aInfectious Disease Institute, Kampala, Uganda

bDivision of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

cDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda

dClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, NCI Campus at Frederick, Frederick

eDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

fDepartment of Public Health and Caring Services, Uppsala University, Uppsala, Sweden

gDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

hGlobal Health Institute, University of Antwerp, Antwerp, Belgium.

Correspondence to William Worodria, MBChB, MMed, PhD, Infectious Disease Institute, PO Box 22418, Kampala, Uganda. E-mail:

Received 25 April, 2018

Revised 6 June, 2018

Accepted 6 June, 2018

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