Changes in the timing of antiretroviral therapy initiation in HIV-infected patients with tuberculosis in Uganda: a study of the diffusion of evidence into practice in the global response to HIV/AIDS.
BACKGROUND
We aimed to determine the extent to which emerging evidence and changing guidelines regarding timing of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected patients with tuberculosis influenced "real-world" clinical practice in Uganda.


METHODS
We evaluated ART-naive, HIV-infected adults starting tuberculosis therapy at 2 HIV clinics in Uganda between 26 August 2006 and 29 September 2012. We used multivariate regression to calculate associations between 4 calendar periods reflecting publication of seminal clinical studies or changes in guidelines and timing of ART after tuberculosis therapy initiation.


RESULTS
For patients with CD4 counts <50 cells/µL, the fraction starting ART within 14 and 30 days of initiating tuberculosis therapy increased from 7% to 14% and from 14% to 86% over the period of observation. The fraction of patients with CD4 counts >50 cells/µL starting ART within 60 days increased from 16% to 28%. After adjustment for sociodemographic factors, when comparing the most recent with the earliest calendar period, the rate of ART initiation increased by 4.57-fold (95% confidence interval [CI], 1.76-fold to 11.86-fold) among patients with baseline CD4 counts ≤ 50 cells/µL and by 5.43-fold (95% CI, 3.16- fold to 9.31-fold) among those with baseline CD4 counts >50 cells/µL.


CONCLUSIONS
We observed large changes in clinical practice during a period of emerging data and changing guidelines among HIV-infected patients with tuberculosis. Nonetheless, a significant proportion of individuals with higher CD4 cell counts do not start ART within recommended time frames. Targeted dissemination and implementation efforts are still needed to achieve target levels in practice.
Division of Infectious Diseases, University of California, San Francisco.
Tara
T
Vijayan
Fred C
FC
Semitala
Nicholas
N
Matsiko
Patrick
P
Elyanu
Jennifer
J
Namusobya
Diane V
DV
Havlir
Moses
M
Kamya
Elvin H
EH
Geng
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D003695:Delivery of Health Care; D005260:Female; D014943:Global Health; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D014454:Uganda / Q000453:epidemiology
D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents
HIV; antiretroviral therapy; diffusion; implementation; tuberculosis