Fanconi-like lab abnormalities reported with daily PrEP: shows importance of routine kidney monitoring

The first case of Fanconi syndrome associated with PrEP was reported in a poster at the 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV. [1]

Diagnosis was based on changes in laboratory tests, without other symptoms, which reversed when PrEP was discontinued. This case was detected during routine monitoring in a prospective phase 4 PrEP study on ways to help adherence. [2]

The case was a 49 year-old man who was otherwise well and who was not taking other medications than daily tenofovir-DF/emtricitabine. His only related medical history included kidney stones seven years earlier.

At screening for the study, creatinine clearance (CrCl) by eGRF was 79.9 which dropped to 68.7 at week 4 and 58.9 at week 12. Additional monitoring showed significantly reduced serum phosphate and increased fractional phosphate excretion (FePi%). These abnormalities are consistent with kidney dysfunction that if allowed to progress would be associated with symptoms linked to Fancoini syndrome.

PrEP was immediately stopped and CrCl returned to near baseline levels over the next 12 weeks, see Table 1. No other abnormalities (glycosuria, haematuria, proteinuria) were detected at any timepoint by dipstick testing.

Table 1: Changes in renal markers linked to early Fanconi syndrome
Timepoint (weeks)	Screening	Wk 4	Wk 12	Wk 16	Wk 18	Wk 21	Wk 24
CrCl (eGFR) ml/min2	79.1	68.7	58.9	69.1	66.6	71.0	74.0
Serum phosphate mg/dL (normal 2.7-4.5)	–	–	1.8	2.7	3.2	2.5	2.8
FePi% (normal 10-20)	–	–	26.6	12.2

Table 1: Changes in renal markers linked to early Fanconi syndrome

Timepoint (weeks)

Screening

Wk 4

Wk 12

Wk 16

Wk 18

Wk 21

Wk 24

CrCl (eGFR) ml/min2

79.1

68.7

58.9

69.1

66.6

71.0

74.0

Serum phosphate mg/dL (normal 2.7-4.5)

–

1.8

2.7

3.2

2.5

2.8

FePi% (normal 10-20)

–

26.6

12.2

Comment

This person had a 25% drop in creatinine clearance and grade 2 hypophosphataemia with increased fractional excretion of phosphate. If there are no other features (proteinuria, glycosuria) there are not enough abnormalities to diagnose Fanconi syndrome (usually at least two of the three abnormalities are required).

This might therefore be a case of renal tubular dysfunction or possible FS/tubulopathy. It is possible that more extensive abnormalities would have developed with ongoing exposure – or that things would have stabilised, but discontinuation was appropriate.

This is an example where TAF (assuming similar efficacy is proven) would clearly be preferred for this patient.

However, the risk of rare side effects reported previously from TDF as HIV treatment, emphasises the importance of routine three-monthly kidney monitoring. If not detected early, symptoms could progress to include extreme fatigue which would hopefully then prompt kidney testing appropriate for PrEP.

Although Fanconi syndrome a serious side effect, this is now rarely reported when tenofovir-DF is used as part of an HIV combination. Early reports were often linked to use with didanosine which is now contraindicated, especially with a boosted protease inhibitor.