Fast disease progression may mean slow immune recovery

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People with HIV who experience fast disease progression with a rapid drop in their CD4 T-cell count may be less likely to regain a normal CD4 level after starting antiretroviral therapy (ART), according to research from the CASCADE Collaboration.

Inma Jarrin from Instituto de Salud Carlos III in Madrid and colleagues looked at trends in CD4 cell recovery and the proportion of people achieving optimal restoration (defined as >500 cells/mm3) after achieving viral suppression on combination ART, comparing those with typical versus unusually rapid CD4 cell declines.

The analysis included 4024 participants in CASCADE Collaboration cohorts. CASCADE is a collaboration of 29 cohorts of people in Europe, Australia, Canada, and Africa with well-estimated dates of HIV seroconversion. Of these, 294 people (7.3%) were classified as rapid progressors, defined as falling below 200 cells/mm3 within a year after seroconversion.

Among people with the same CD4 count at baseline, rapid progressors saw significantly faster CD4 cell increases during the first month on ART compared to typical progressors. But after the first month and continuing through month 18, the rapid progressors had slightly slower CD4 cell increases compared to typical progressors. From month 18 through month 60, there were no significant differences in CD4 cell recovery according to progression category.

Overall, rapid progressors were significantly less likely to achieve optimal CD4 cell levels than typical progressors at month 12 (29.2% vs 62.5%) and month 36 (47.1% vs 72.4%). By month 60, there was no longer a significant difference (70.4% vs. 71.8%, respectively). However, these significant differences disappeared after adjusting for baseline CD4 cell level, with odds ratios of 0.86, 0.90, and 1.56, respectively, at months 12, 36, and 60.

Based on these findings, the researchers concluded, “Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4 T-cell counts than non-rapid progressors, but are less likely to achieve optimal restoration during the first 36 months after combination ART, mainly because of lower CD4 T-cell counts at c combination ART initiation.”

Objective: This article compares trends in CD4+ T-cell recovery and proportions achieving optimal restoration (≥500 cells/μl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors.
Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4+ less than 200 cells/μl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration.
Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4+ T-cell count at cART start (baseline), rapid progressors experienced faster CD4+ T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1–18 [−0.05 (−0.06; −0.03)] and no significant differences in 18–60 months [−0.003 (−0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4+ T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively.
Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4+ T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4+ T-cell counts at cART initiation.

HIV and Hepatitis material
AIDS abstract

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