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Predictors of HIV Disease Progression in Patients Who Stop ART with CD4 Cell Counts >350 cells/mm3
Daniel Skiest*1, D Havlir2, R Coombs3, E Adams4, P Cain5, T Petersen6, D Rusin7, C Jennings8, K Robertson9, D Margolis9, and the ACTG 5170 Team
1Baystate Med Ctr, Springfield, MA, US; 2Univ of California, San Francisco, US; 3Univ of Washington, Seattle, US; 4NIAID, NIH, DHHS, Bethesda, MD, US; 5Stanford Univ Med Ctr, CA, US; 6Univ of Texas Southwestern Med Ctr, Dallas, US; 7Frontier Sci & Tech Res Fndn, Amherst, NY, US; 8Rush Presbyterian/St Luke's Med Ctr, Chicago, IL, US; and 9Univ of North Carolina at Chapel Hill, US
Background: HIV-infected patients often interrupt ART
because a of toxicity, treatment fatigue, or other
factors. We studied disease progression and the predictive value of virologic and immunologic factors in subjects stopping ART.
We sought to determine the safety of interruption and to identify parameters
that would define patients in whom ART interruption was of low risk.
Methods: ACTG 5170 was a multicenter, prospective study
of HIV-infected patients with CD4 cell count >350 cells/mm3 prior
to ART and within 45 days of study entry, HIV RNA viral load <55,000 copies/mL within 45 days of study entry, and on ART (≥2
drugs) for ≥6 months. Subjects stopped ART at entry and were followed for
96 weeks. ART was restarted at the discretion of the patient and health care
provider. The primary endpoint was time to CDC Category B or C event or death
or CD4 count ≤250 cells/mm3.
Results: We enrolled 167 subjects. The median entry
CD4 count was 833 cells/mm3 and 136 subjects
had viral load ≤400 copies/mL. The median nadir CD4 count was 436 cells/mm3 (IQR 375 to 510). The median time
on ART was 3.9 years and the median number of cumulative adverse reactions was
3 (range, 3 to 9). The median length of ART interruption was 96 weeks. CD4 cell
decline following ART cessation occurred in 2 phases: 198 cells/mm3 in
the first 8 weeks, then 1.74 cells/mm3 per week, from week 8
through 96. The median time to reaching viral load set-point off ART was 4.3 weeks
(IQR 3.1 to 8.4 wks). Following ART cessation, 1 subject had the acute
retroviral rebound syndrome and 4 subjects had thrombocytopenia (platelet count
<55,000). A possible or definite CDC category B or C diagnosis occurred in 3
and 2 subjects, respectively (all with CD4 >350 cells/mm3). At 96
weeks, 17 patients had confirmed CD4 count ≤250 cells/mm3
and 46 subjects had restarted ART. During the study, 5 subjects died, but no
death was related to HIV/AIDS diagnoses. Of 28 subjects, 24 with viral load
≤400 copies/mL at entry, and who restarted ART
achieved a viral load of ≤400 copies/mL. In univariate analysis, shorter time to primary endpoint at
week 48 and 96 was predicted by low CD4 count nadir, lower entry CD4 count
entry, and higher entry viral load. In multivariate analysis only CD4 nadir was
predictive (p = 0.049). Activated CD4
or CD8 phenotype at entry correlated with greater CD4 decline at week 96 (p <0.05).
Conclusions: ART interruption was generally safe in
this cohort. Low nadir CD4 count is
the best predictor of CD4 decline or clinical events following ART cessation.
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