Clinical predictors of immune reconstitution following combination antiretroviral therapy in patients from the australian HIV observational database

Reena Rajasuriar, Maelenn Gouillou, Tim Spelman, Tim Read, Jennifer Hoy, Matthew Law, Paul U. Cameron, Kathy Petoumenos, Sharon R. Lewin

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29 Scopus citations

Abstract

Background: A small but significant number of patients do not achieve CD4 T-cell counts >500cells/μl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods: Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500cells/μl, HIV RNA<500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500cells/μl and >200cells/μl. Results: 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32-47) years and 236 (130-350) cells/μl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3-10) years. Most patients (80%) achieved CD4 T-cell counts >500cells/μl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500cells/μl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500cells/μl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200cells/μl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001). Conclusion: The time taken to achieve a CD4 T-cell count >500cells/μl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500cells/μl.

Original languageEnglish
Article numbere20713
JournalPLoS ONE
Volume6
Issue number6
DOIs
StatePublished - 2011
Externally publishedYes

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