Immuno‐virological discordance is associated with a higher frequency of AIDS, severe non‐AIDS, and death
Authors: Zoufaly A , Cozzi‐Lepri A , Kirk O , Lundgren J , Reiss P , van Lunzen J , Mocroft A 
Published: November 2012

Persistent immunosuppression despite viral suppression (immunovirological discordance, ID) has been associated with higher risk of AIDS and death, although the risk for AIDS seems to decrease with longer time of suppressed viral load (sVL). The impact of ID on a composite endpoint of AIDS/serious non‐AIDS/death has not been thoroughly investigated. Patients in EuroSIDA starting ≥1 new antiretroviral drugs after January 2001, when CD4 was <200 cells/mm3 and VL >500 copies/mL, and who achieved a sVL ≤50 copies/mL within 1 year were included. Person‐years of follow‐up (PYFU) accrued from the date of sVL until the first of a new AIDS or severe non‐AIDS (SNA) event or death, viral rebound >50 copies/mL (first of 2 consecutive values) or last visit. Rate ratios (RR) were calculated using Poisson regression according to whether or not patient's current CD4 count was still below 200 cells/mm3 (ID). Models were stratified according to whether or not persons were ART‐naïve at baseline. Multivariable models included age, HBV/HCV status, mode of HIV transmission, race, cohort, anemia, diabetes, hypertension or current eGFR, current cART, number of previous antiretrovirals, and time to viral suppression. 994 patients satisfied the inclusion criteria and contributed 4520 PYFU. Median age was 41 (IQR 34–47) years and 72.8% were male. 36.5% of patients were ART‐naïve and started a median of 3 (IQR 2–3) new drugs. 31 AIDS and 58 non‐AIDS events occurred, and 31 patients died (7 due to AIDS, 24 due to SNA). The rate of the combined endpoint in patients with ID (50.3 per 1000 PYFU [95% CI 35.2–69.9]) was higher than in patients recovered from ID (22.1 [17.6–27.3], adjusted RR 2.08 [1.32–3.28]; table). This was similar regardless of whether or not people were ART‐naïve before starting a new drug (interaction test p=0.47). In ID, rate was highest in the first 6 months of sVL (63.1 [33.6–107.9]) and declined thereafter (month 6–12: 60.5 [26.1–119.2],>12 months: 39.8 [22.2–65.6], adjusted RR compared to month 0–6 0.52 [0.24–1.13]). In analyses with endpoints AIDS/death due to AIDS and SNA/death due to SNA separately, the adjusted RR of ID vs. non ID was 4.11 ([1.76–9.60]; p=0.001) and 1.46 ([0.81–2.61]; p=0.207), respectively.

Exposure
No.events
PYFU
Rate (95%CI)
Crude RR (95%CI)
Adjusted**RR (95%CI)

All patients

No Discordance
84
3805
22.1 (17.6–27.3)
1
1

Discordance
36
716
50.3 (35.2–69.6)
2.28 (1.54–3.38)
2.08 (1.32–3.28)

ART‐naïve* patients

No Discordance
29
1324
21.9 (14.7–31.5)
1
1

Discordance
9
228
39.5 (18.1–74.9)
1.80 (0.84–3.85)
1.87 (0.81–4.33)

ART‐treated* patients

No Discordance
55
2481
22.2 (16.7–28.9)
1
1

Discordance
27
488
55.4 (36.5–80.6)
2.50 (1.67–3.97)
1.89 (1.08–3.32)

before starting a new antiretroviral drug according to the inclusion criteria, p(test for interaction):0.47
adjusted for smoking, HBV/HCV coinfection, transmission risk, race, cohort, current cART, change of ART before viral suppression, time to viral suppression, presence of diabetes, hypertension, anemia, current eGFR <90, CD4 nadir, CD4 count and viral load at baseline.

ID is a risk factor for clinical disease progression particularly related to AIDS events. In patients with ID, we found a trend for a declining incidence of events with longer periods of sVL, suggesting that sustained viral suppression might be of benefit.