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  4th IAS (Intl AIDS Society) Conference on HIV Pathogenesis, Treatment and Prevention
Sydney, Australia
22-25 July 2007
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Treatment Breaks Boosted Bacterial Pneumonia Risk in SMART Trial
 
 
  4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention
July 22-25, 2007
Sydney, Australia
 
Mark Mascolini
 
People who took CD4 count-guided drug breaks in the SMART trial [1] had more than a 50% higher risk of bacterial pneumonia than people who stayed on treatment [2]. Statistical analysis showed that lower CD4 counts and higher viral loads in the treatment interruption (TI) group explained their higher pneumonia risk. But other factors--notably smoking--also made pneumonia more likely in the study group as a whole.
 
SMART randomized mostly treatment-experienced people to keep taking their antiretrovirals steadily or to suspend treatment whenever the CD4 count stood at or above 350, then to restart when the count dropped under 250. The trial stopped early when researchers counted significantly more AIDS and serious non-AIDS diagnoses in the TI group [1].
 
Among 5472 SMART participants monitored for an average 16.2 months, clinicians diagnosed bacterial pneumonia in 115 of them, 70 in the TI arm and 45 in the steady-treatment arm. Pneumonia rates per 100 patient-years proved significantly higher in the TI group (2.0) than in the control arm (1.2) (P = 0.02). Eight people in the TI group had recurrent bacterial pneumonia for a rate of 0.2 cases per 100 patient-years, compared with 3 people in the steady-treatment group for a rate of 0.1, but that difference stopped short of statistical significance (P = 0.14).
 
CD4 counts just before pneumonia diagnosis averaged 460 in the TI group versus 603 in the continuous-therapy group, a significant difference (P = 0.005). Among treatment interrupters with bacterial pneumonia, 25.7% had a viral load below 400 copies just before diagnosis, compared with 51.1% in the control arm (P = 0.006).
 
Multivariate analysis determined that the risk of bacterial pneumonia was 60% higher in people who took drug breaks, 82% higher in smokers, 59% higher in past smokers, 51% higher in injecting drug users, 48% higher among blacks (versus whites), and more than doubled in people with earlier recurrent bacterial pneumonia. But the risk comparisons involving former cigarette smokers, injecting drug users, and blacks fell short of statistical significance:
 
- TI versus steady therapy: hazard ratio (HR) 1.60, P = 0.01
- Smoker (yes versus no): HR 1.82, P = 0.02
- Former smoker: HR 1.59, P = 0.10
- Injecting drug user (yes versus no): HR 1.51, P = 0.08
- Black versus white: HR 1.48, P = 0.07
- Prior recurrent pneumonia (yes versus no): HR 2.61, P < 0.01
 
Pretreatment CD4 count, lowest-ever CD4 count, pretreatment viral load, and gender did not affect the risk of bacterial pneumonia.
 
When SMART statisticians adjusted this analysis for latest CD4 count and viral load before pneumonia diagnosis, the higher risk in the TI group virtually disappeared. That meant latest CD4 tally and viral load almost completely explained the higher pneumonia risk in the drug-holiday group versus the steady-treatment group. For the whole study group, the risk of bacterial pneumonia slipped 8% for every 100-cell higher CD4 count.
 
The SMART team concluded that "smoking cessation programs should be a part of routine HIV care" and that "sustained use of antiretroviral drugs needs to be emphasized with patients as an important means to reduce the occurrence of [bacterial pneumonia,] one of the most commonly reported clinical events" with HIV.
 
References
1. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296.
2. Gordin F, Roediger M, Clezy K, et al. An increased risk of bacterial pneumonia in patients interrupting antiretroviral treatment: results from the SMART study. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract MOPEB100.