The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression

Background: The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression. Methods: A total of 3,780 patients from the EuroSIDA study under follow-up after 2001 with a current CD4(+) T-cell count <= 200 cells/mm(3) were stratified into five groups: group 1, viral load (VL)<50 copies/ml on cART; group 2, VL 50-99,999 copies/ml on cART; group 3, VL 50-99,999 copies/ml off cART; group 4, VL >= 100,000 copies/ml on cART; and group 5, VL >= 100,000 copies/ml off cART. Poisson regression was used to identify the risk of (non-fatal or fatal) AIDS-and non-AIDS-related events considered together (AIDS/non-AIDS) or separately as AIDS or non-AIDS events within each group. Results: There were 428 AIDS/non-AIDS events during 3,780 person-years of follow-up. Compared with group 1, those in group 2 had a similar incidence of AIDS/non-AIDS events (incidence rate ratio [IRR] 1.04; 95% CI 0.79-1.36). Groups 3, 4 and 5 had significantly higher incidence rates of AIDS/non-AIDS events compared with group 1; incidence rates increased from group 3 (IRR 1.78; 95% CI 1.25-2.55) to group 5 (IRR 2.36; 95% CI 1.66-3.40), demonstrating the increased incidence of AIDS/non-AIDS events associated with increasing viraemia. After adjustment, the use of cART was associated with a 40% reduction in the incidence of AIDS/non-AIDS events in patients with VL 50-99,999 copies/ml (IRR 0.59; 95% CI 0.41-0.85) and in those with a VL>100,000 copies/ml (IRR 0.66; 95% CI 0.44-1.00). Similar relationships were seen for non-AIDS events and AIDS events when considered separately. Conclusions: In patients with ongoing severe immunosuppression, cART was associated with significant clinical benefits in patients with suboptimal virological control or virological failure.