TY - JOUR
T1 - Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries
T2 - a prospective, observational study
AU - Centers for AIDS Research Network of Integrated Clinical Systems
AU - on behalf of the
AU - HIV-CAUSAL Collaboration
AU - the
AU - Caniglia, Ellen C.
AU - Cain, Lauren E.
AU - Sabin, Caroline A.
AU - Robins, James M.
AU - Logan, Roger
AU - Abgrall, Sophie
AU - Mugavero, Michael J.
AU - Hernández-Díaz, Sonia
AU - Meyer, Laurence
AU - Seng, Remonie
AU - Drozd, Daniel R.
AU - Seage, George R.
AU - Bonnet, Fabrice
AU - Dabis, Francois
AU - Moore, Richard D.
AU - Reiss, Peter
AU - van Sighem, Ard
AU - Mathews, William C.
AU - del Amo, Julia
AU - Moreno, Santiago
AU - Deeks, Steven G.
AU - Muga, Roberto
AU - Boswell, Stephen L.
AU - Ferrer, Elena
AU - Eron, Joseph J.
AU - Napravnik, Sonia
AU - Jose, Sophie
AU - Phillips, Andrew
AU - Justice, Amy C.
AU - Tate, Janet P.
AU - Gill, John
AU - Pacheco, Antonio
AU - Veloso, Valdilea G.
AU - Bucher, Heiner C.
AU - Egger, Matthias
AU - Furrer, Hansjakob
AU - Porter, Kholoud
AU - Touloumi, Giota
AU - Crane, Heidi
AU - Miro, Jose M.
AU - Sterne, Jonathan A.
AU - Costagliola, Dominique
AU - Saag, Michael
AU - Hernán, Miguel A.
N1 - Funding Information:
ECC reports grants from the National Institutes of Health (NIH) during the study. LEC reports grants from NIH during the study; and other from Takeda Pharmaceuticals, outside the submitted work. CAS reports grants from NIH and UK MRC to fund the UK Collaborative HIV Cohort (UK CHIC) study during the study; personal fees from Gilead Sciences, ViiV Healthcare. SH-D is an epidemiologist for the North American AED Pregnancy Registry, which is funded by AbbVie, Concordia, Novartis, Janssen, Pfizer, Sunovion, and UCB; and is an adviser for the National Pregnancy Registry for Atypical Antipsychotics, which is supported by AstraZeneca, Bristol-Myers Squibb/Otsuka, Ortho-McNeil Janssen, and Sunovion. LM reports grants from ANRS during the study; and grants from ANRS, Sidaction Fondation de la Recherche Medicale, and European FP7 through the UK MRC, outside the submitted work. DRD reports personal fees from Gilead Sciences, outside the submitted work; and adviser for the Massachusetts General Hospital antipsychotics pregnancy registry. FB reports personal fees from Gilead, ViiV Healthcare, MSD, Bristol-Myers Squibb, Pierre Fabre, Janssen, and Novartis; and grants from Gilead to the Aquitaine Cohort. RDM reports grants from the NIH during the study. PR reports grants and other from Gilead Sciences, Janssen Pharmaceutical, and ViiV Healthcare; and grants from Bristol-Myers Squibb and Merck & Co, outside the submitted work. AvS reports grants from the Dutch Ministry of Health, Welfare and Sport, during the conduct of the study; grants from the European Centre for Disease Prevention and Control; and personal fees from ViiV Healthcare, Gilead Sciences, and Janssen-Cilag, outside the submitted work. WCM reports grants from the NIH during the study. JdA reports research grants awarded from Bristol-Myers Squibb, Gilead, and ViiV Healthcare. EF reports personal fees from Janssen, Gilead, and MSD for advisory board or lectures. JJE reports grants from the NIH during the study; grants and personal fees from Bristol-Myers Squibb, Gilead Sciences, Janssen, and ViiV Healthcare; and personal fees from Merck outside the submitted work. SN reports grants from the NIH during the study. SJ reports grants from UK Medical Research Council (MRC) during the study; and personal fees from Gilead Sciences Ltd, outside the submitted work. APh reports personal fees from Gilead, outside the submitted work. ACJ reports grants from NIH National Institute on Alcohol Abuse and Alcoholism during the study; and grants from Janssen-Cilag, outside the submitted work. JG reports grants from NIH during the conduct of the study; and personal fees from Merck, Gilead, and ViiV Healthcare, outside the submitted work. HF reports grants paid to his institution from ViiV; and grants from Gilead, MSD, Janssen, BMS, and AbbVie, outside the submitted work. KP reports personal fees from ViiV Healthcare, outside the submitted work. HC reports grants from NIH and Patient-Centered Outcomes Research Institute, outside the submitted work. JMM reports grants and personal fees from AbbVie, Bristol-Myers Squibb, Medtronick, Merck Novartis, and VIIV Healthcare, outside the submitted work. JAS reports grants from UK MRC during the study. DC reports personal fees and other from Gilead; personal fees from Innavirvax; grants, personal fees and other from Janssen; grants and personal fees from MSD; and grants and other from ViiV Healthcare, outside the submitted work. MS reports grants from CNICS R24 and from NIH, during the study; grants from Merck, Bristol-Myers Squibb, Gilead, ViiV Healthcare, and AbbVie; and personal fees from Merck, BMS, and Gilead, outside the submitted work. MAH reports grants from the NIH during the study. JMR, RL, SA, MJM, RS, GRS, FD, SM, SGD, RM, SLB, JPT, APa, VGV, HCB, ME, and GT declare no competing interests.
Funding Information:
This research was supported by the NIH ( grant number R01 AI073127 ); by the National Institute of Allergy and Infectious Diseases (grant number T32 AI007433); and by the CFAR Network of Integrated Clinical Systems (CNICS), an NIH funded programme that was made possible by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI; grant number R24 AI067039). The contents of this Article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. JMM received a personal intensification research grant (number INT15/00168) from Instituto de Salud Carlos III, Madrid, Spain.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/6
Y1 - 2017/6
N2 - Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 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 HR was 1·05 (95% CI 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) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.
AB - Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 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 HR was 1·05 (95% CI 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) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.
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U2 - 10.1016/S2352-3018(17)30043-7
DO - 10.1016/S2352-3018(17)30043-7
M3 - Article
C2 - 28411091
AN - SCOPUS:85017444979
VL - 4
SP - e251-e259
JO - The Lancet HIV
JF - The Lancet HIV
SN - 2352-3018
IS - 6
ER -