Immune restoration and onset of new AIDS-defining events with combination antiretroviral therapy in HIV type-1-infected immigrants in the Netherlands

Abstract

Background: We investigated differences in immune restoration and onset of new AIDS-defining events on combination antiretroviral therapy (cART) among HIV type-1 (HIV-1)-infected patients of different regional origin now living in the Netherlands.

Methods: Treatment-naive adults reaching plasma viral load (pVL)<400 copies/ml within 9 months of starting cART were selected from the Netherlands ATHENA cohort. CD4(+) T-cell response on cART was determined over 7 years using mixed models. CD4(+) T-cell counts were excluded from the analyses at the first of two consecutive measurements of pVL≥400 copies/ml following prior suppression to <400 copies/ml. Multivariate analyses included gender, age, CD4(+) T-cell count and pVL prior to cART, hepatitis coinfection, HIV-1 transmission and region of origin (Western Europe/North America [WN], sub-Saharan Africa [SSA], Southeast Asia [SEA], Latin America/Caribbean [LAC] or other).

Results: For 6,057 selected patients (WN 3,947, SSA 989, SEA 237, LAC 695 and other 189), median follow-up was 3.2 years (WN 3.3, SSA 2.9, SEA 3.2, LAC 2.7 and other 2.7). CD4(+) T-cell increase in the first 6 months of cART was lower in males than females (-26 cells/mm(3); P<0.0001) and in patients from SSA compared with WN (-36 cells/mm(3); P<0.0001). Because men from SSA started with lower CD4(+) T-cell counts than men from WN, they continued to lag behind and had lower absolute CD4(+) T-cell counts after 7 years of cART. Furthermore, cumulative tuberculosis incidence after 7 years of cART was higher in SSA compared with WN (4.5% versus 0.5%, hazard ratio 5.08, 95% confidence interval 2.22-11.60).

Conclusions: HIV-1-infected immigrants from SSA have blunted immune restoration on fully suppressive cART and should be identified at an earlier disease stage. Our results call for more intensive screening for both latent and active tuberculosis in these patients.