When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries

Caniglia, Ellen C; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernández–Dı́az, Sonia; Meyer, Laurence; Seng, Rémonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, François; Moore, Richard; Reiss, Peter; Sighem, Ard van; Mathews, William C; Amo, Julia del; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; José, Sophie; Phillips, Andrew; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A C; Costagliola, Dominique; Saag, Michael S.; Hernán, Miguel A.

doi:10.1097/qai.0000000000000956

Cited by 22 publications

(18 citation statements)

References 19 publications

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“…While these studies found no clinical harm for annual 13–17 or biannual 11,12 monitoring, further follow-up is needed to establish the long-term safety. Moreover, none of these studies evaluated the effectiveness of the dynamic monitoring strategies recommended by the guidelines with respect to virologic and clinical outcomes.…”

Section: Introductionmentioning

confidence: 92%

“…Two randomized trials 11 , 12 and several observational studies, 13 – 16 including ours, 17 focused on CD4 cell and HIV-RNA monitoring strategies in which monitoring frequency is independent of an individual’s time-varying CD4 cell count. While these studies found no clinical harm for annual 13 – 17 or biannual 11 , 12 monitoring, further follow-up is needed to establish the long-term safety. Moreover, none of these studies evaluated the effectiveness of the dynamic monitoring strategies recommended by the guidelines with respect to virologic and clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

et al. 2017

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BackgroundClinical 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.MethodsWe 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.Findings47,635 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.InterpretationOur 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.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

et al. 2017

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“…In fact, an individual's data at baseline may be consistent with more than one of the four strategies of interest. As previously described in detail, we solved this problem by creating an expanded data set with four exact replicates of each individual (one per strategy), each following one of the strategies of interest. We censored each replicate, as described above, when the individual's data were no longer consistent with the strategy assigned to the replicate.…”

Section: Estimating the Per‐protocol Effectmentioning

confidence: 99%

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV‐positive individuals

Robins

Cain

Sabin

et al. 2019

Statistics in Medicine

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Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen?We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency 2428

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“…This paper3 by the HIV-CAUSAL collaboration across several centres in UK and Europe looked at clinical, immunological and virological outcomes when monitoring at 3, 6 or 9–12 months in resource-rich settings. They looked at data from 39 029 antiretroviral naive patients starting on therapy, who became undetectable within 12 months of starting therapy and then followed them up for 24 months for the two clinical outcomes (all-cause mortality and a combined endpoint of AIDS-defining illness or death) and 18 months for virological outcomes (HIV RNA >200 copies/mL and CD4 count).…”

Section: When To Monitor Cd4 and Hiv Viral Loadmentioning

confidence: 99%

Clinical round-up

Herbert¹

2018

Sex Transm Infect

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When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 22 publications

References 19 publications

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV‐positive individuals

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