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ART soon after infection linked to better CD4 recovery through 10 years
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from Jules: Early ART within 3 months of infection results in 85% of patients achieving optimal immune reconstitution (OIR) (defined by a CD4>800 cells/mm3 or CD4%>40% or CD4/CD8 ratio>1) vs 53% in patients who started ART in chronic infection, after 1 year with infection
CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
Starting antiretroviral therapy (ART) within 3 months of HIV seroconversion led to better CD4 recovery by several measures compared with starting ART during chronic infection [1]. The difference between the early-ART group and the later-ART group persisted through 10 years of follow-up.
Sabine Kinloch-de Loes and colleagues at University College London noted that starting ART early delays time to AIDS. But less is known about whether ART begun soon after HIV infection has immunologic benefits over the long term.
To address that question, they conducted this retrospective study of people who began ART within 3 months of seroconversion at London's Royal Free Hospital. Everyone had taken continuous ART for at least 5 years. Kinloch and colleagues compared them with a group that started ART during chronic infection at a CD4 count above 350 and continued uninterrupted treatment for at least 5 years. The researchers compared immunologic changes in the two groups by several measures--CD4 count, CD4 percent, CD4/CD8 ratio, and "optimal immune reconstitution," defined as a CD4 count at or above 800, a CD4 percent at or above 40%, or a CD4/CD8 ratio at or above 1.
The study involved 37 people treated early and 115 first treated in chronic infection. Median ages of the early and later ART groups were 34 and 32, 94.6% and 87% were men, and 86.5% and 73% were men who have sex with men. Median pre-ART nadir CD4 count, CD4 percent, and CD4/CD8 ratio in the early and later groups stood at 417 versus 313, 18% versus 16%, and 0.30 versus 0.29. Median (and range) maximum pre-ART viral load were 511,000 copies (3400 to more than 1 million) in the early ART group and 278,022 copies (2593 to more than 750,000) in the later ART group.
Median CD4 count 1, 5, and 10 years after ART began remained significantly greater through 10 years in the early-ART group than in the later-ART group: 743 versus 600 (P < 0.0001), 850 versus 779 (P = 0.005), and 966 versus 874 (P = 0.02). Median CD4 percents at 1, 5, and 10 years were also significantly greater in people who started ART soon after seroconversion: 35% versus 26% (P < 0.0001), 39% versus 33% (P < 0.0001), and 38% versus 33% (P = 0.01).
Proportions of people who achieved optimal immune reconstitution proved significantly greater in the early-ART group than the later-ART group after 1 year of ART (51% versus 25%, P = 0.002), 5 years of ART (73% versus 46%, P = 0.003), and 10 years of ART (85% versus 53%, P = 0.003). Median CD4/CD8 ratio reached a significantly higher mark in the early-ART group after 1 year of therapy (0.95 versus 0.52, P < 0.001), after 5 years (1.05 versus 0.78, P < 0.001), and after 10 years (1.09 versus 0.85, P = 0.04). Median time to reaching a CD4/CD8 ratio above 1.0 was 36 weeks (95% confidence interval 16 to 63) in the early-ART group versus 187 weeks (95% confidence interval 127 to 204) in the later-ART group (P < 0.0001).
The persistence of immunologic differences through 10 years of ART, the researchers proposed, suggests "damage to the immune system during early stages of HIV infection can result in long-term consequences."
Reference
1. Kinloch S, Smith C, Tsz-Shan K, Ellis J, Johnson M. Enhanced immune reconstitution with initiation of ART at HIV-1 seroconversion (PHI). CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 335. For e-poster: www.croiconference.org/sites/default/files/posters-2015/335.pdf
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Reported by Jules Levin
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