Methods: Longitudinal data on clinical events, surrogate markers and health utilities collected by the OPTIMA study (an ongoing trial of treatment strategies for patients with advanced HIV disease for whom standard therapies have failed) were analyzed. An increase of 50 cells/mm3 from baseline CD4 count and a 0.50 log drop from baseline pVL were considered as immunologic and virologic responses, respectively. We fitted generalized linear models (estimated using GEE) to examine the determinants of utilities assessed by Health Utilities Index Mark-3 (HUI3). Time-dependent covariates included immunologic response, virologic response only (or neither), presence of SAEs and ADIs, and time in years, all adjusted by baseline utility, CD4 and pVL.
Results: Among the 363 patients enrolled as of March, 2006 (mean age: 48 years, male: 98%, median follow-up time: 2-years), 505 SAEs (fatal/life-threatening: 13%, hospitalized: 81%) had occurred in 170 patents, and 91 ADIs in 64 patients. At baseline, patients had a mean log10 pVL=4.8, CD4=126 cells/mm3 and HUI3=0.59. Among the 193 patients who made the 48-week visit, 62 (32%) showed immunologic response while 41 (21%) had a virologic response only. In the multivariate model, immunologic and virologic response (CD4 improvement: 0.05, p<0.01, pVL improvement only: 0.03, p<0.01), presence of SAEs (-0.13, p<0.01) and ADIs (-0.09, p<0.01) were all important predictors of patients' utilities.
Conclusions: We found that health utilities among patients with advanced HIV disease were substantially affected by SAEs, independent of virologic and immunologic response and ADIs. Due to their frequency and associated costs, we propose that economic models of late stage disease should incorporate SAEs explicitly.