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Original article

CD4+ T-cell-guided structured treatment interruptions of antiretroviral therapy in HIV disease: projecting beyond clinical trials

Yazdan Yazdanpanah, Lindsey L Wolf, Xavier Anglaret, Delphine Gabillard, Rochelle P Walensky, Raoul Moh, Christine Danel, Caroline E Sloan, Elena Losina, Kenneth A Freedberg, the CEPAC-International Investigators

Corresponding author name: Yazdan Yazdanpanah
Corresponding author e-mail: yyazdan@yahoo.com

Citation: Antiviral Therapy 2010; 15:351-361
doi: 10.3851/IMP1542

Date accepted: 23 November 2009
Date published online: 26 May 2010

Abstract

Background: International trials have shown that CD4+ T-cell-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4+ T-cell interruption/reintroduction thresholds than those assessed in actual trials.

Methods: Using a model of HIV, we simulated cohorts of African adults with different baseline CD4+ T-cell counts (≤200; 201–350; and 351–500 cells/μl). We varied ART initiation criteria (immediate; CD4+ T-cell count <350 cells/μl or ≥350 cells/μl with severe HIV-related disease; and CD4+ T-cell count <200 cells/μl or ≥200 cells/μl with severe HIV-related disease), and ART interruption/reintroduction thresholds (350/250; 500/350; and 700/500 cells/μl). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line therapy was protease inhibitor (PI)-based.

Results: STI generally reduced life expectancy compared with continuous ART. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48–69 and 11–30 months compared with continuous ART when interruption/reintroduction thresholds were 350/250 and 500/350 cells/μl, depending on ART initiation criteria. When patients interrupted/reintroduced ART at 700/500 cells/μl, life expectancies ranged from 2 months lower to 1 month higher than continuous ART. STI-related life expectancy increased with decreased risk of virological resistance after ART interruptions.

Conclusions: STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4+ T-cell thresholds (700/500 cells/μl) and use first-line medications with higher resistance barriers, such as PIs.

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