Forty-nine patients (9-18 year old) were studied. They had a mean age of 13.6 years, and 28 (57%) were female. The mean CD4% value was 27.1 (± 10.2), corresponding to value of 565 cells/μL; 47% had HIV-RNA undetectable, and 39% of patients had a history of CDC (Center for Disease Control) class C clinical diagnosis, and no patients had creatinine > 1 mg/dL at baseline. None of the patients was treatment naive.
Sixty-three percent were treated with antiretroviral (ARV) regimens containing Tenofovir (Group A: TDF), and 37% without TDF (Group B: No TDF).
Forty-seven percent were treated with regimens containing both TDF and PI (Group C: TDF+PI), and 53% without this combination (Group D: No TDF+PI). Specifically, 16% of patients were on TDF without PI, 20% were with PI but alternative NRTIs, and 16% with other regimens containing neither TDF nor PI. The children didn't differ for age, gender, frequency of undetectable HIV-RNA, or ethnicity (p > 0.05 for all comparisons) both between Group A and Group B, and between Group C and D. CD4 resulted lower in group A and Group C if compared to Group B and D respectively (Table ).
Baseline characteristics of the patients, overall and in each treatment group
As shown in Figure , in the entire cohort there was a significant increase of serum creatinine, from a median of 0.62 mg/dL at baseline to 0.73 mg/dL (p < 0.0001) after 2 years; eGFR decrease from a median of 143.6 at baseline to 135.6 at 1 year, and 128.9 ml/min per 1.73 m2 at 2 years (p = 0.006). The value of phosphatemia decreased significantly from 4.4 at baseline to 4.0 at 1 year (p = 0.0301) and to 3.8 mg/dl at 2 years (p = 0.0003). The median of potassiemia in the entire cohort during the study period didn't vary significantly.
Figure 1 Renal function and tubular damage markers, at baseline and after 1 and 2 years, in the entire cohort, and in each treatment group. Patients were grouped according to the exposure to antiretrovirals: Group A = TDF, Group B = no TDF; Group C = TDF+PI, Group (more ...)
The creatinine increased significantly after 2 years in each of the groups analyzed, from +0.10 in Group A and C to +0.16 mg/dL in Group B. There were no significant differences between Group A and B, and Group C and D.
The eGFR decreased after 2 years in all groups, significantly in Group B (-23.8 ml/min per 1.73 m2, p = 0.012) and Group D (-19.1, p = 0.02). There were no significant differences between Group A and B, and Group C and D. Among the subgroups we observed that 7 patients on TDF+PI, 2 on PI and not in TDF, 1 in TDF and not PI, and 2 not taking nor TDF nor PI showed an increase in eGFR during the study period. On the other hand only 1 patient on TDF remained stable and all the others (37 patients) showed a decrease in eGFR. Three patients developed a mild reduction in glomerular filtration rate (60-89 ml/min per 1.73 m2), all were treated with both TDF and PI. Among these patients none received any other nephrotoxic drugs during the entire study period and none of them experienced infections or malignancy.
The phosphatemia decreased after 2 years in each group, significantly in Group A (-0.5 mg/dL, p = 0.0058) and Group C (-0.5, p = 0.0128). There were no significant differences between Group A and B, and Group C and D. Five patients developed a grade 1 or 2 DAIDS hypophosphatemia event; among these, 4 were treated with TDF+PI and one only with TDF. Phosphorus levels came back to normal without discontinuing the therapy. Among these patients two were HCV co infected, not taking any HCV treatment, and one patient experienced Burkitt Lymphoma and underwent chemotherapy.