Work

On the assessment of trend in CD4+ cell count and viral suppression after transition to adult care

Year: 2019

Type: letter

Abstract: The article by Xia et al.[1] on the effects of transition from paediatric to adult care on retention in HIV care, viral suppression, CD4+ cell count, and mortality among individuals with perinatal HIV infection in New York City offers insight into an interesting and increasingly important topic in HIV clinical care and research. Their primary conclusions were that rates of viral suppression and the number of individuals with a CD4+ cell count at least 500 cells/μl significantly increased after transition to adult care. However, their other primary conclusion was that 1-year mortality was significantly higher post-transition. These conclusions from the same study are not logically consistent. If viral suppression and CD4+ cell counts are increasing, mortality should be decreasing. These discordant findings could be a result of selection bias due to the authors’ follow-up definition. For the assessment of the retention in care, viral suppression, and CD4+ cell count outcomes, a trend analysis using generalized estimating equations was utilized. Individuals were included if they transitioned from paediatric to adult care during 2006–2015 and had at least 1 year of pretransition follow-up. The post-transition follow-up continued for 3 years after transition, until death, or until the end of the study period on 31 December 2016, whichever occurred first. The trend analysis limited assessment of CD4+ cell count and viral suppression to those who completed 3 years of follow-up and did not die during the study. Therefore, the analysis excluded anyone who died during the study or transitioned after 31 December 2013, as those would be unable to contribute 3 years of follow-up. Of the 735 individuals who transitioned during 2006–2015 and had at least 1 year of pretransition follow-up, 76 individuals died overall and 41 died within the first year after transition. Among the 41 who died in the first year after transition, 34 (82.9%) died from HIV-related diseases. There are several concerns with the design of the study to assess the retention in care, CD4+ cell count, and viral suppression post-transition outcomes. First, if the 76 individuals died during the study had lower rates of viral suppression and lower CD4+ cell counts compared with those who survived 3 years of post-transition follow-up, the exclusion of these individuals from the post-transition analyses could lead to positively biased inferences, a result of the healthy survivor effect. This bias is likely, as those who died in the first-year post-transition had lower rates of pretransition viral suppression (12.2% vs. 47.8%) and lower proportion of higher CD4+ cell counts (2.4% vs. 37.2%) compared with those who survived. Similarly, those who transitioned later in calendar time but were excluded from the analysis may have had higher rates of viral suppression and higher CD4+ cell counts as antiretroviral therapy prescription and viral suppression have been shown to improve over time in the United States [2,3]. Exclusion of these individuals could lead to negatively biased inferences. In addition, Xia et al. [1] do not describe how missing laboratory results were handled in the study. Retention in care was defined by the presence of at least one lab value during the year of interest. Those who were not retained in care were still included in the trend analysis for viral suppression and CD4+ but, if lab values were missing, it is unclear how viral suppression and CD4+ outcomes were determined. One option would be to impute the missing values. A second option would be to carry the last observation forward, although this strategy would likely overestimate viral suppression and CD4+ cell counts, as those who are lost to care are more likely to have unsuppressed viral loads and lower CD4+ cell counts. The third option would be to assume that those with missing values had unsuppressed viral loads and low CD4+ cell counts; however, this strategy may underestimate viral suppression and CD4+ cell counts if these individuals had transferred and were not actually lost to care. The transition from paediatric to adult HIV care is increasingly important, and these findings suggest that transition to adult care increases viral suppression and CD4+ cell counts, which would imply that this transition leads to improved HIV outcomes. However, if its inferences are biased, this study could lead to an underestimation of the risks inherent in this important transition. Studies addressing this topic should take care in defining their exclusion criteria (which may induce selection biases) and explaining their handling of missing data, to accurately characterize this critical transition. Acknowledgements This work was supported by the National Institutes of Health (R01 MH113438, PI-Pettit) (K01 AI131895, PI-Rebeiro) and the National Institute of Health funded Tennessee Center for AIDS Research (P30 AI110527). This work was also supported by Clinical Translational Science Award No. UL1TR000445 and Clinical Translational Science Award No. TL1TR002244 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Conflicts of interest There are no conflicts of interest.

Source: AIDS

DOI: 10.1097/qad.0000000000002226

Authors: Cassandra Oliver, Peter F. Rebeiro, April C. Pettit

Institution: Vanderbilt University

Language: English

Topic: HIV/AIDS Research and Interventions

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green