The effect of AIDS Clinical Trials Group Protocol 5164 on the time from Pneumocystis jirovecii pneumonia diagnosis to antiretroviral initiation in routine clinical practice: a case study of diffusion, dissemination, and implementation

Abstract

Background: Diffusion, dissemination, and implementation of scientific evidence into routine clinical practice is not well understood. The Adult AIDS Clinical Trials Group (ACTG) Protocol 5164 showed that early antiretroviral therapy (ART; ie, within 14 days) after diagnosis of an opportunistic infection improved clinical outcomes, compared with later initiation. Subsequently, the San Francisco General Hospital (SFGH) HIV/AIDS Service performed the SFGH 5164 Initiative to disseminate and implement the findings of ACTG 5164.

Methods: We evaluated patients who received a diagnosis of Pneumocystis jirovecii pneumonia (PCP) from 1 January 2001 through 30 March 2011. Survival analyses were used to assess changes in the time to initiation of ART after PCP, and logistic regression was used to evaluate changes in the odds of early ART (ie, within 14 days) because of ACTG 5164 and SFGH 5164 Initiative.

Results: Among 162 patients, the adjusted hazard of ART initiation increased by 3.05 (95% confidence interval [CI], 1.86-5.02) after ACTG 5164 and by 4.89 (95% CI, 2.76-8.67) after the SFGH Initiative, compared with before ACTG 5164. When compared with before ACTG 5164, the proportion of patients who received ART within the 14 days after PCP diagnosis increased from 7.4% to 50.0% (P < .001) after ACTG 5164 and from 50.0% to 83.0% (P = .02) after the SFGH 5164 Initiative.

Conclusions: Diffusion of findings from of a randomized trial changed practice at an academic medical center, but dissemination and implementation efforts were required to establish early ART at acceptable levels. Early ART initiation can be achieved in real-world patient populations.

Figure 1.

Time to antiretroviral therapy initiation after diagnosis of Pneumocystis jirovecii pneumonia (PCP).

Figure 2.

Proportion of patients per calendar year who initiated antiretroviral therapy (ART) early (defined as <14 days after Pneumocystis jirovecii pneumonia diagnosis). The total number of patients per year is shown across the top of the figure.

Figure 3.

Time to first HIV RNA level <400 copies/mm³ after antiretroviral therapy initiation.