Early switching of tenofovir disoproxil fumarate (TDF) in HIV-infected patients with TDF-induced nephrotoxicity: a prospective study

Figures & data

Figure 1 Flow diagram of eligible cases.

Table 1 Baseline characteristics and pre-switch laboratory markers in the two groups

Baseline characteristics	Early-switching (n = 19)	Late-switching (n = 14)	p-value
Age	52.68 ± 11.28	50 ± 12.57	0.52
Sex
Male, n (%)	15 (78.9)	11 (78.6)	>0.99
Female, n (%)	4 (21.1)	3 (21.4)
Body weight, kg	59.58 ± 11.98	63.56 ± 10.75	0.33
Nadir CD4, cells/mm^3	74 (27–212)	125 (52.25–504.75)	0.13
Nadir CD4, %	7 (2–14)	5.5 (4–16)	0.55
Pre-switch CD4, cells/mm^3	417.37 ± 204.8	504.86 ± 258.55	0.29
Pre-switch CD4, %	20.53 ± 7.63	22.21 ± 9.06	0.57
Previous opportunistic infection, n (%)	9 (47.7)	6 (42.86)	>0.99
Cryptococcal infection	2	2
Tuberculosis	5	1
Endemic dimorphic fungus	2	1
Other	0	2^‡
Comorbidity, n (%)	14 (73.68)	12 (85.71)	0.67
Type-II diabetes mellitus	3 (15.8)	3 (21.43)	>0.99
Hepatitis C infection	2 (10.53)	2 (14.29)	>0.99
Hypertension	6 (31.6)	5 (35.71)	>0.99
Duration of TDF exposure, months	73.53 ± 32.59	83.21 ± 31.05	0.40
Pre-switch HAART, n (%)
FTC + TDF + EFV	18 (94.7)	12 (85.7%)	0.48
3TC + TDF + NVP	1 (5.3)	1 (7.1%)
FTC + TDF + NVP	0 (0)	1 (7.1%)
Switch regimen, n (%)
ABC + 3TC + EFV	10 (52.6)	11 (78.6%)	0.13
3TC + LPV/r	9 (47.4)	3 (21.4%)
Pre-switch laboratory parameters
Urinary β2-microglobulin, µg/L	870 (230–2,700)	19,840 (1,350–21,700)	0.005^†
Hypophosphatemia, n (%)	3 (15.8)	2 (14.3)	0.99
Low TmP/GFR, n (%)	11 (57.9)	10 (71.4)	0.42
Normoglycemic glycosuria, n (%)	2 (10.5)	8 (57.1)	0.007^†
FEUP, %	17.38 (11.95–23.38)	20.82 (16.02–43.22)	0.06
TmP/GFR, mg/dL	2.6 (2.31–3.08)	2.68 (1.43–2.98)	0.16
Serum phosphate, mg/dL	3.21 ± 0.65	3.01 ± 0.68	0.41
FEUA, %	10.93 (8.8–15.1)	14.48 (10.11–41.03)	0.06
UPCI, mg/g creatinine	175.88 (110–280)	875 (195.5–1,475)	0.005^†
Pre-TDF creatinine, mg/dL	0.95 ± 0.26	0.83 ± 0.2	0.15
Pre-TDF eGFR, mL/min/1.73 m^2	96.91 ± 18.89	108.14 ± 19.42	0.11
Pre-switch creatinine, mg/dL	1.06 ± 0.21	1.4 ± 0.28	<0.001^†
Pre-switch eGFR, mL/min/1.73 m^2	85.09 ± 15.37	61.51 ± 18.67	<0.001^†
eGFR change, %	−11.27 (−19.12 to −8.62)	−41.29 (−50.34 to −35.73)	<.001^†
Lipid profile
Total cholesterol, mg/dL	223.39 ± 44.88	189.33 ± 36.38	0.04^†
HDL, mg/dL	47.39 ± 8.86	43.17 ± 14.61	0.70
Triglyceride, mg/dL	145.5 (114–226.75)	168.5 (91.5–199.25)	0.98
LDL, mg/dL	139.5 (107.5–151.5)	109 (87.5–132.25)	0.03^†

^‡ Cytomegalovirus retinitis and cerebral toxoplasmosis.

^† Significant.

TDF = Tenofovir disoproxil fumarate; HAART = highly active antiretroviral therapy; FTC = emtricitabine; 3TC = lamivudine; NVP = nevirapine; EFV = efavirenz; ABC = abacavir; LPV/r = lopinavir/ritonavir; TmP = tubular maximum reabsorption of phosphate; GFR = glomerular filtration rate; FEUA = fractional excretion of uric acid; UPCI = urinary protein–creatinine index; HDL = high-density lipoprotein; LDL = low-density lipoprotein.

Figure 2 Kaplan–Meier survival curves comparing probability of no complete recovery between the two groups.

Survival analysis performed using Kaplan–Meier survival curves and log-rank test.

Figure 3 Changes in tubular function markers from pre-switch levels to 3, 6, and 12 months after switching [mean ± SD (95% CI)]. (A) Estimated glomerular filtration rate (eGFR); (B) tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR); (C) fractional excretion of urinary phosphate (FEUP); (D) fractional excretion of uric acid (FEUA); and (E) urinary protein-creatinine index (UPCI).

Repeated-measures ANOVA was used to calculate change for each urinary marker during the follow-up within each group. Pairwise comparisons at each time point were made using repeated-measures ANOVA with Bonferroni’s correction for multiple comparisons.

Striped light-gray box = early-switching group.

Dark-gray box = late-switching group.

Dashed line = cutoff of normal value.

*Significant.

Table 2 Changes in tubular markers, CD4, and lipid profile from the pre-switch value to 6 and 12 months after switching

Change in tubular markers (12 months: pre-switch value)	Early-switching	Late-switching	p-value (between groups)
Δ eGFR (mL/min/1.73 m^2)	3.68 (95% CI: −4.07 to 11.43)	6.29 (95% CI: −4.29 to 16.87)	0.001†
Δ FEUP (as absolute change in %)	−7.8 (95% CI: −12.68 to −2.93)	−13.4 (95% CI: −28.24 to 1.438)	0.02†
Δ TmP/GFR (mg/dL)	0.47 (95% CI: 0.127 to 0.807)	0.37 (95% CI: −0.95 to 1.69)	0.09
Δ FEUA (as an absolute change in %)	−4.27 (95% CI: −7.24 to −1.3)	−12.47 (95% CI: −29.24 to 4.3)	0.05
Δ UPCI (mg/g creatinine)	−33.81 (95% CI: −210.17 to 142.55)	−338.6 (95% CI: −1,406.96 to 729.76)	0.001†
CD4 change (6 months: pre-switch value)	Early-switching	Late-switching
Δ CD4 (cell/mm^3)	37.39 (95% CI: −5.44 to 80.22)	−10 (95% CI: −66.86 to 46.86)	0.53
Δ CD4 (%)	1.33 (95% CI: 0.19 to 2.48)	2.07 (95% CI: 0.72 to 3.42)	0.65
Change in lipid profile (12 months: pre-switch value)	Early-switching	Late-switching
Δ Total cholesterol (mg/dL)	35.17 (95% CI: 6.28 to 64.05)	44 (95% CI: 18.32 to 69.68)	0.65
Δ HDL (mg/dL)	2.28 (95% CI: −2.02 to 6.58)	18.25 (95% CI: −5.3 to 41.8)	0.20
Δ Triglyceride (mg/dL)	106.11 (95% CI: 34.41 to 177.81)	60.6 (95% CI: 17.25 to 103.95)	0.90
Δ LDL (mg/dL)	7.27 (95% CI: −16.92 to 31.47)	28.82 (95% CI: 4.20 to 53.43)	0.06
New treatment, increasing dose or change of lipid-lowering agent due to an increase in the lipid profile, n (%)	7/17 (41.18%)	6/13 (46.15%)	>0.99

Repeated-measures ANOVA was used to calculate changes for each urinary marker and lipid parameter from pre-switch to 12-months post-switch, and for CD4 level and CD4 percentage changes from pre-switch to 6-month post-switch. The effect between ESG and LSG groups was compared using repeated-measures ANOVA.

^† Significant.

eGFR = estimated glomerular filtration rate; CI = confidence interval; FEUP = fractional excretion of urinary phosphate; TmP = tubular maximum reabsorption of phosphate; GFR = glomerular filtration rate; FEUA = fractional excretion of uric acid; UPCI = urinary protein–creatinine index; HDL = high-density lipoprotein; LDL = low-density lipoprotein.