Characteristics and Outcomes of Cytomegalovirus Infection in Seropositive Kidney Transplant Recipients in the Era of Antiviral Prophylaxis with Valacyclovir: A Single-Center Study in Morocco

Figures & data

Figure 1 Flow chart.

Table 1 Characteristics of Patients with Detectable DNAemia and Those with Quantifiable DNAemia

Characteristics	Total (n= 38)	With Detectable DNAemia (n = 8)	With Quantifiable DNAemia (n = 30)	P-value
Age (years); mean (SD)	36.6 ± 13.19	40.3 ± 18.53	35.6 ± 11.58	0.37
Donor status, (n, %)
Living	29 (76.3)	6 (75.0)	23 (76.7)	1.00
Deceased	9 (23.7)	2 (25.0)	7 (23.3)
Blood transfusion history, (n, %)
No	21 (56.8)	2 (25.0)	19 (65.5)	0.055
Yes	16 (43.2)	6 (75.0)	10 (34.5)
HLA-AB mismatch, (n, %)
1–4	33 (89.2)	8 (100.0)	25 (86.2)	0.56
0	4 (10.8)	0(0.0)	4 (13.8)
HLA-DR mismatch, (n,%)
1 –2	30 (83.3)	7 (87.5)	23 (82.1)	1
0	6 (16.7)	1 (12.5)	5 (17.9)
Duration of prophylactic treatment (days); mean (SD)	118.7 ± 48.13	107.3 ± 28.43	121.7 ± 52.11	0.46
Time of active replication after transplantation (days); mean (SD)	173.6 ± 117.18	294.1 ± 112.6	141.5 ± 96.9	< 0.001*
Active replication at prophylactic period treatment, (n, %)
No	24 (63.2)	8 (100.0)	16 (53.0)	0.017*
Yes	14 (36.8)	0(0.0)	14 (47.0)
Time of active replication after prophylactic treatment (days); mean (SD)	95.8 ± 86.25	166.7 ± 118.33	78.1 ± 70.34	0.064
Coinfection, (n,%)
No	28 (73.7)	7 (87.5)	21 (70.0)	0.65
Yes	10 (26.3)	1 (12.5)	9 (30)

Note:

* P < 0.05 was statistically significant.

Abbreviations: SD, standard deviation; HLA, human leukocyte antigen.

Table 2 Characteristics of Patients with Asymptomatic CMV Infection and Those with CMV Disease

Characteristics	Total (n = 30)	With Asymptomatic CMV Infection (n= 22)	With CMV Disease (n = 8)	P-value
Recipient age at transplantation; mean (SD)	35.6 ± 11.58	38.1 ± 12.34	28.8 ± 5.12	0.007*
Donor source, (n, %)
Living	23 (76.7)	18 (81.8)	5 (62.5)	0.34
Deceased	7 (23.3)	4 (18.2)	3 (37.5)
HLA-AB mismatch, (n,%)
1–4	25 (86.2)	19 (86.4)	6 (85.7)	1
0	4 (13.8)	3 (13.6)	1 (14.3)
HLA-DR mismatch, (n, %)
1 –2	23 (82.1)	18 (85.7)	5 (71.4)	0.57
0	5 (17.9)	3 (14.3)	2 (28.6)
Induction therapy, (n, %)
Thymoglobulin	26 (86.7)	19 (86.4)	7 (87.5)	1
Basiliximab	4 (13.3)	3 (13.6)	1 (12.5)
Creatinine level (mg/l) at 3 months of monitoring; mean (SD)	11.2 ± 4.16	11.2 ± 4.07	11.2 ± 4.65	0.99
Creatine clearance rate (mL/min/1.73 m^2) at 3 months of monitoring; mean (SD)	78.7 ± 23.13	77.7 ± 21.53	81.3 ± 28.21	0.71
Duration of prophylactic treatment (days); mean (SD)	124.9 ± 47.04	138.5 ± 35.89	146.2 ± 34.87	0.60
Antiviral prophylaxis, (n, %)
Valaciclovir	26 (86.7)	20 (90.9)	6 (75.0)	0.39
Valganciclovir	3 (10.0)	2 (9.1)	1 (12.5)
Valaciclovir follow-up valganciclovir	1 (3.3)	0(0.0)	1 (12.5)
Mean CMV viral load at diagnosis (log UI/mL), SD	2.3 ± 1.19	2.1 ± 0.74	2.9 ± 1.91	0.29
Duration of appearance reactivation after kidney transplantation (days); mean (SD)	132.9 ± 84.10	130.3 ± 75.93	140.1 ± 109.20	0.78

Note:

* P < 0.05 was statistically significant.

Abbreviations: CMV, cytomegalovirus; SD, standard deviation; HLA, human leukocyte antigen; UI, unit international.

Table 3 Characteristics of Patients with Asymptomatic DNAemia and Those with Disease DNAemia

Characteristics	Total With Asymptomatic (n = 30) DNAemia (n = 22)	With Disease DNAemia (n = 8)	P-value
Peak viral load (log 10 IU/mL), mean (SD)	2.74 ± 1.21 2.4 ± 0.79	3.8 ± 1.59	0.003*
Duration of onset viral load peak after kidney transplantation (days), mean (SD)	153.8 ± 83.78 140.5 ± 77.13	190.2 ± 95.72	0.15
Duration of quantifiable DNAemia (days), median (range)	42.5 (1–1280) 13.4 (1–55)	21.2 (1–1280)	0.028*
Duration of curative treatment (days), median (range)	12.3 (15–55) 12.3 (15–30)	24.3 (21–55)	< 0.001*
Antiviral treatment, (n, %)
Valaciclovir	1(8.3) 1(20.0)	0(0.0)	0.49
Valganciclovir	1(8.3) 0 (0.0)	1(14.0)
Ganciclovir	10 (83.3) 4 (80.0)	6 (86.0)
Coinfections, (n, %)
Negative	19 (63.3) 17 (77.3)	2 (25.0)	0.028 *
Positive	11 (36.7) 5 (22.7)	6 (75.0)
Acute rejection, (n, %)
No	26 (86.7) 22 (100.0)	4 (50.0)	0.003*
Yes	4 (13.3) 0 (0.0)	4 (50.0)

Note:

* P < 0.05 was statistically significant.

Abbreviation: SD, standard deviation.

Table 4 Analysis of Risk Factors of Reactivation/Reinfection in Seropositive Kidney Transplant Recipients with Quantifiable DNAemia and Their Clinical Symptoms (D+/R+)

Variables	CMV Reactivation/Reinfection Total (n = 38)		Reactivation/Reinfection with Quantifiable DNAemia (n = 30)		Reactivation/Reinfection with Clinical Symptomatic DNAemia (n = 8)
	Odds Ratio (95% CI)	P-value	Odds Ratio (95% CI)	P-value	Odds Ratio (95% CI)	P-value
Age of recipients at transplantation (years)	0.96 (0.92–1.00)	0.08	0.97 (0.92–1.03)	0.36	0.92 (0.83–1.01)	0.07
Donor age (years)	0.98 (0.95–1.02)	0.37	1.00 (0.95–1.06)	0.96	0.99 (0.93–1.05)	0.70
Deceased donor	3.10 (0.61–15.91)	0.17	0.91 (0.15–5.58)	0.92	2.7 (0.45–16.26)	0.28
Number of HLA-DR mismatch	2.86 (0.83–9.82)	0.09	0.66 (0.07–6.61)	0.72	0.42 (0.05–3.22)	0.40
Blood transfusion history	0.81 (0.27–2.41)	0.70	5.7 (0.97–33.60)	0.05	3.56 (0.61–20.81)	0.16
Time of active replication after transplantation (days)	NA	NA	0.98 (0.98–0.99)	0.004*	1 (0.99–1.01)	0.76
Viral load at diagnosis (log10 IU/mL)	NA	NA	NA	NA	1.71 (0.83–3.50)	0.14
Mean Peak viral load (log10 IU/mL)	NA	NA	NA	NA	3.39 (1.21–9.53)	0.02*
Antiviral prophylaxis	0.50 (0.14–1.8)	0.29	0.46 (0.07–3.13)	0.43	3.38 (0.58–19.60)	0.18
Length of primary prophylaxis (days)	0.99 (0.98–1.00)	0.16	1.01 (0.99–1.02)	0.45	1.03 (0.99–1.06)	0.06

Notes:

* P < 0.05 was statistically significant using univariate logistic regression. In application of univariate analysis, we identified that time of active replication was factor risk of development of quantifiable DNAemia with P= 0.004 and peak viral load was associated with occurrence of symptomatic DNAemia, P=0.02.

Abbreviations: CMV, cytomegalovirus; D+, seropositive donor; R+, seropositive recipient; HLA, human leukocytes antigen; IU, international unit; NA, not applicable.

Figure 2 Kaplan–Meier survival evaluation in kidney transplant recipients who remained free from CMV disease during prophylaxis treatment. A significant difference was observed between the two groups (Log- Rank test, P= 0.004).

Figure 3 Kaplan–Meier survival evaluation in kidney transplant recipients who remained free from acute rejection throughout the follow-up period. No significant difference was observed between the two groups (Log- Rank test, P = 0.12).

Figure 4 Kaplan–Meier survival evaluation in patients who remained free of acute rejection throughout the follow-up period. A significant difference was observed between the two groups (Log Rank test, P = 0.001).