Influence of Prior Structured Treatment Interruptions on the Length of Time without Antiretroviral Treatment in Chronically HIV-Infected Subjects

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Abstract
The influence of previous structured treatment interruptions (STIs) on the length of time off therapy when highly active antiretroviral treatment (HAART) is discontinued in chronically HIV-infected subjects was assessed. A comparative, retrospective clinical cohort study included patients with plasma viral load (VL) 500 cells/mm3 who interrupted HAART. Fifteen patients interrupted HAART after six 2-weeks-off-/4-weeks-on therapy cycles (STI group) and 30 subjects discontinued HAART without previous STIs (NSTI group). The criteria for treatment resumption were development of AIDS-defining clinical events, VL >100,000 copies/ml or CD4 3. Median (IQR) time off therapy was 48 (29–56) weeks in the STI group and 31 (8–77) weeks in the NSTI group (p < 0.15). After 48 weeks, 46% of the patients in the STI group and 40% in the NSTI group remained off HAART (p < 0.74). No patient developed AIDS-defining events and all but one achieved virological control after treatment resumption. The CD4 nadir was 341 (298–464) cells/mm3 among patients who reinitiated HAART and 560 (364–682) cells/mm3 in those who remained off therapy by week 48 (p 3 and 1123 (924–1234) cells/mm3 in subjects resuming and remaining off HAART, respectively (p = 0.03). No relationship between treatment resumption and pre-ART VL or with the time with undetectable VL before enrolment was found. CD4 nadir was a significant predictor for treatment reinitiation in a multivariate analysis. Previous STIs do not influence time off therapy when HAART is definitively discontinued in chronically HIV-infected subjects. CD4 nadir is an important factor in the treatment discontinuation decision.