Reading Response Discussions

Exposure: depression, anxiety, and stress in after HIV-seroconversion 

Outcome: time to cognitive decline among adults with HIV

Lifecourse model: Social trajectories as well as accumulation of risk, whereby risks are primarily mediated by a succession of harmful social exposures. This aligns with the theory of syndemics, which is increasingly being applied to HIV research. Using this framework, I would hypothesize that levels of depression, anxiety, and/or stress in combination with new HIV infection may increase the likelihood of earlier cognitive decline through multiple biological and psychosocial pathways. 

Regression model: I think that a model for time-to-decline incorporating interactions between co-occurring psychosocial and structural problems to represent accumulation of risk from stress and/or long term exposure to material adversity would be appropriate. Literature on syndemics suggests that interactions should be studied using models that suggest synergy, rather than additive associations with the outcome. A 'fully saturated linear regression model could be appropriate to capture all possible interactions between variables (Tsai,. & Venkataramani, 2016). Mediation analysis might also be helpful.

 Y = α + β₁X₁ + β₂X₂ + β₃X₃ + β₄X₁X₂ + β₅X₁X₃ + β₆X₂X₃ + β₇X₁X₂X₃

Data set: Multicenter AIDS Cohort Study (MACS) public data set. This public dataset has been released from CAMACS (Center for Analysis and Management of Multicenter AIDS Cohort Study) since 1994. The data comprise baseline and 6 month follow-up interview data, including medical history, behavior, SF36, physical examination data, frailty measurements, neuropsychology tests, and concurrent laboratory test results, and summary files of HIV status and medical events.

Concerns about interpretation:

One concern would be that people who have a history of depression/anxiety/stress would be more likely to seek medical care and therefore more likely be diagnosed with cognitive impairment at earlier stages (aka selection bias).

I would also be concerned about cohort effects due to the different types of ART medications that individuals may have been exposed to (with increasing advances in medication safety and tolerability over time).

Additionally, based on my understanding of the current clinical literature, it may take many years (even decades) for depression to manifest in and/or increase risk for dementias in the general population. Therefore, I would be hesitant to make definitive statements from data that did not follow participants for a substantial length of time.

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