Comparing dynamic monitoring strategies based on evolving CD4 cell counts in virologically suppressed HIV-positive individuals on cART : a prospective observational study in high-income countries

Abstract

Altres ajuts: This research was supported by NIH grant R01 AI073127; by NIH grant T32 AI007433 from the National Institute of Allergy and Infectious Diseases; and by the CFAR Network of Integrated Clinical SystemsCNICS, an NIH funded program (R24 AI067039) that was made possible by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung and Blood Institute (NHLBI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on evolving CD4 cell counts in virologically suppressed HIV-positive individuals. We used data from prospective studies of HIV-positive individuals in Europe and the Americas in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies, which differ with respect to the CD4 cell count threshold that is used to measure CD4 cell count and HIV-RNA every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the thresholds 200, 350, and 500 cells/μl. We estimated hazard ratios of death and of AIDS-defining illness or death, risk ratios of virologic failure, and mean differences in CD4 cell count using inverse probability weighting to adjust for baseline and time-varying confounders. 47,635 eligible individuals initiated a cART regimen between January, 2000 and November, 2015 and met the eligibility criteria for our study. During follow-up, CD4 cell count and HIV-RNA were measured on average every 4 and 3.8 months, respectively. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1,091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality hazard ratio (95% CI) was 1.05 (0.86, 1.29) for threshold 200 and 1.02 (0.91, 1.14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95, 1.22) and 1.03 (0.96, 1.12), respectively. The respective 24-month risk ratios (95% CI) of virologic failure (HIV-RNA>200 copies/ml) were 2.01 (1.17, 3.43) and 1.24 (0.89, 1.73) and 24-month mean CD4 cell count differences (95% CIs) were 0.4 (−25.5, 26.3) cells/μl and −3.5 (−16.0, 8.9) cells/μl. Our findings suggest that decreasing monitoring to annually when CD4 cell count>200 cells/μl compared with >500 cells/μl does not worsen the short-term clinical and immunologic outcomes of virologically suppressed HIV-positive individuals, but more frequent virologic monitoring may be necessary to decrease the risk of virologic failure. Further follow-up is needed to establish the long-term safety of these strategies.