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CD4 Gains During Suppressive Therapy Differ by Pretreatment T-Cell Count
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9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow
Mark Mascolini
Two retrospective studies [1,2] bolstered earlier cohort results [3,4] showing that people who start antiretrovirals with more than 350 cells have the best chance of reaching a normal CD4 count. But the smaller of the two studies also yielded some optimistic results for people who begin treatment with a sub-200 count and keep viral replication under wraps [2]. Although both analyses focus on patients from single centers and suffer from possible confounding seen in nonrandomized studies, they suggest that viral suppression for 5 years or more continues to pay immunologic dividends--especially in people who begin therapy with a higher T-cell quotient.
Clinicians from an HIV clinic in Perugia, Italy retrospectively analyzed 352 consecutive adults who kept their viral load below 400 copies for at least 6 months after starting their first combination regimen [1]. Follow-up reached at least 1 year in every individual and stretched up to 8 years. Treatment duration averaged 56.2 months.
The investigators defined a normal CD4 tally as one above 700 and stratified patients into three groups according to pretreatment count: under 200 (n = 172, 49%), 200 to 350 (n = 85, 24%), and above 350 (n = 95, 27%).
After 5 years of antiretroviral therapy, 29%, 62%, and 82% in the three CD4 strata had a count above 350 (P = 0.034). Only people who began therapy with more than 350 CD4s reached a normal CD4 count within 4 years. Among people starting therapy with fewer than 200 cells, CD4 counts continued to rise through 8 years of follow-up without reaching the normal threshold of 700 cells. Pretreatment viral load, gender, and type of antiretroviral regimen did not influence CD4 recovery. Coinfection with hepatitis C virus correlated with a lower CD4 count 7 years after starting therapy (P = 0.041).
People who were older than 49 when they took their first antiretrovirals and had a pretreatment count below 200 gained CD4 cells more slowly than their younger counterparts. But age did not appear to affect immunologic response in older people who started antiretrovirals with more than 200 CD4s.
University of New South Wales investigators tracked CD4 changes in 56 men and 3 women who kept their viral load under 400 copies for at least 5 years [2]. Median pretreatment CD4 count measured 238 (interquartile range [IQR] 120 to 360), and median pretreatment viral load stood at 50,000 copies. Median treatment duration reached 7.6 years (IQR 5.9 to 9.3). The researchers estimated a "CD4 set point" as the point at which a person's CD4 slope became 0, in other words, the point at which a person appeared to stop gaining T cells.
A CD4 graph for all cohort members discerned two patterns--a gradually rising CD4 count that began to level off after about 6 years of therapy, and constantly rising CD4s. People with the latter pattern had a higher pretreatment CD4 count, lower pretreatment viral load, and no AIDS diagnosis. Forward stepwise multivariate analysis isolated pretreatment HIV RNA as the sole predictor of a consistently rising CD4 count.
Twenty-four people (41%) reached a CD4 set point, which came at a median of 616 cells (IQR 579 to 789) for people who began therapy with fewer than 200 CD4s and at a median of 880 cells (IQR 696 to 1057) for people who started with more than 350. However, these findings suggest that, after 7 years of treatment, people who begin therapy with a CD4 count under 200 stand a 50-50 chance of getting their counts back to 600 and that many get their counts into the 700s.
Pretreatment CD4% was significantly higher in people who reached a CD4 set point than in those who did not (20% versus 13%, P < 0.01).
The Australian cohort is much smaller than the Italian group, but their follow-up is longer. An array of differences in demographics, treatment practices, and study design also undoubtedly contribute to the differing results.
References
1. Malincarne E, Sgrelli A, Camanni G, et al. Immune restoration during HAART: 8-year follow-up in HIV-positive patients with sustained virologic suppression. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract P010.
2. Byakwanga H, Murray JM, Petoumenos K, et al. Evolution of CD4+ T-cell count in HIV-1 infected adults receiving antiretroviral therapy with sustained long-term virological suppression. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract P070.
3. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441-446.
4. Gras L, Kesselring AM, Griffin JT, et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm(3) or greater. J Acquir Immune Defic Syndr. 2007;45:183-192.
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