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Shorter Treatment Breaks, More Regimens
Predict Complete CD4 Response in 10 Years
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IAS 2015, July 19-22, 2015, Vancouver
Mark Mascolini
Using more antiretroviral regimens [from Jules: perhaps this represents quicker switching after viral load rebound and/or more attention to following patient & doing labs rather than too infrequent labs] and having shorter treatment interruptions independently predicted a complete CD4 response in a French cohort that started a protease inhibitor (PI) regimen in 1997-1999 [1]. One third of this group had study-defined incomplete CD4 response, and 80% had an incomplete CD4 or CD4/CD8 ratio response after 10 years of follow-up.
Failure to reach a normal CD4 count after years of suppressive antiretroviral therapy (ART) persists in the current treatment era. But reasons for an intractably subnormal CD4 response remain elusive. To address this issue, APROCO-COPILOTE investigators studied cohort members who had at least 10 years of follow-up and a good virologic response after starting a PI in 1997-1999. They defined incomplete CD4 response as a count at or below 500 at the end of follow-up and incomplete CD4 or CD4/CD8 response as a count at or below 500 or a ratio at or below 1 at the end of follow-up. They defined a treatment sequence as a different line of therapy, with each change representing a new line.
The cohort included 399 people (81% men) who met selection criteria: viral load below 50 copies at last visit and no more than 1 viral blip between 50 and 500 copies in the last 18 months. Median pre-ART age stood at 39 years, median pre-ART CD4 count measured 254, and 39% had a pre-ART count below 200. Median pretreatment viral load measured 4.6 log10 (about 40,000 copies). The highest proportions of cohort members started ART with indinavir (45%) or nelfinavir (32%).
Among the 399 people in this group, 132 (33%) had an incomplete CD4 response and 319 (80%) and an incomplete CD4 or CD4/CD8 response. Logistic regression analysis identified four factors that independently predicted incomplete CD4 response at 10 years, at the following odds ratios (OR) (and 95% confidence intervals):
-- Baseline age at or above 40: OR 2.55 (1.57 to 4.12), P < 0.001
-- CD4 count at month 4 at or below 500: OR 2.79 (1.21 to 6.41), P = 0.016
-- CD4 count at month 12 at or below 500: OR 3.56 (1.81 to 6.99), P < 0.001
-- Total ART interruption duration 3 months or more: OR 2.32 (1.17 to 4.58), P < 0.016
Five factors predicted incomplete CD4 or CD4/CD8 response at 10 years:
-- CD4/CD8 ratio at month 8 at or below 0.8: OR 6.14 (2.21 to 17.1), P < 0.001
-- CD4/CD8 ratio at month 12 at or below 0.8: OR 5.53 (2.18 to 14.0), P < 0.001
-- Total ART interruption duration 3 months or more: OR 4.44 (1.41 to 13.9), P = 0.011
-- 4 to 6 ART sequences (vs fewer): OR 0.33 (0.14 to 0.75), P = 0.008
-- 10 or more ART sequence (vs fewer): OR 0.19 (0.06 to 0.62), P = 0.006
The French team noted that their findings confirm the baneful effects of treatment interruptions. They observed that short-term changes in CD4 count and CD4/CD8 ratio proved strong predictors of 10-year immunologic changes, but pretreatment CD4 count did not predict 10-year CD4 or CD4/CD8 response.. The researchers suggested that the beneficial effect of more antiretroviral sequences could reflect faster shifts from failing combinations and/or physician willingness to substitute newer, stronger, less toxic regimens for older combinations.
Reference
1. Raffi F, Perrier A, Le Moing V, et al. Factors associated with incomplete immunologic recovery in HIV-infected patients with clinical and virologic success after 10 years of antiretroviral therapy: a prospective cohort study. IAS 2015. 8th Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2015. Vancouver. Abstract MOPEB149.
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