- Renal function is estimated by the modified Cockgraft-Gault or modification of diet in renal disease (MDRD) formulae.
- For haemodialysis, the ART prescribed should be taken after dialysis.
In HIV-positive patients on chronic haemodialysis, there are a number of important ART considerations. The NRTI class is eliminated through the kidneys, thus most NRTIs require dose adjustment as per Table 25. For suggested TDF dosing in patients with chronic hepatitis B see Module 20.
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|TABLE 25: Antiretroviral drug dose adjustments in renal failure.†|
|Drug||CrCl§,¶||Haemodialysis (dosage after dialysis)||Peritoneal dialysis|
|10–50 mL/min||< 10 mL/min|
|TDF||Avoid||Avoid||300 mg once weekly||Unknown|
|3TC||150 mg daily||50 mg daily‡||50 mg first dose, thereafter 25 mg daily‡||50 mg first dose, thereafter 25 mg daily‡|
|AZT||Unchanged||300 mg daily||300 mg daily||300 mg daily|
3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; AZT, zidovudine; CrCl, creatinine clearance; d4T, stavudine; ddI, didanosine; eGFR, estimated glomerular filtration rate; InSTIs, integrase strand transfer inhibitors; MDRD, modification of diet in renal disease; NNRTIs, non-nucleoside reverse transcriptase inhibitors; PIs, protease inhibitors; NRTIs, nucleoside reverse transcriptase inhibitors; sCr, serum creatinine; TDF, tenofovir disoproxil fumarate.
‡, Some experts recommend that the lowest available tablet dose of 150 mg 3TC daily be used in patients with advanced renal disease (CrCl < 10 mL/min) and patients on dialysis so as to avoid having to use the liquid formulation of 3TC, and because of the favourable safety profile and lack of data to suggest 3TC dose-related toxicity. This is particularly relevant if the 3TC liquid formulation is unavailable or not tolerated.
§, The modified Cockgraft-Gault equation: CrCl = (140 – age × ideal weight) ÷ sCr. For women, multiply the total by 0.85.
¶, Many laboratories report the eGFR calculated using a variation of the MDRD formula. This result can be used (in place of the calculated CrCl) to make decisions regarding the use of TDF and for modification of the dose of other NRTIs based on this table.
Antiretroviral drug choice and dosing in patients on chronic haemodialysis
- Patients with HIV may develop end-stage renal failure owing to HIV-associated nephropathy or an HIV-unrelated cause, necessitating chronic haemodialysis.
- TDF can be used in patients on chronic haemodialysis, but with once-weekly dosing which can be difficult for patients to remember.
- AZT is generally avoided because of anaemia associated with renal failure.
- InSTIs and NNRTI drugs do not require dose adjustment.
- ATV concentrations are reduced in patients on haemodialysis to a greater degree than LPV concentrations.
- LPV/r requires twice-daily dosing in patients on haemodialysis.
- ART drugs taken once daily, or the evening doses of drugs taken twice daily, should be given after the haemodialysis session on dialysis days, to prevent the drug from being dialysed out.
- Patients on chronic haemodialysis should be reviewed by a clinician experienced in ART management at least 6-monthly, to monitor treatment efficacy and side-effects and to adjust the regimen when needed.
We recommend the following first-line option for patients on chronic haemodialysis: ABC (600 mg daily) + 3TC (50 mg first dose and thereafter 25 mg daily) + DTG (50 mg daily). On the days when haemodialysis is performed, the drugs should be given after the haemodialysis session.
|Common pitfall: Not giving daily doses or the evening doses of a twice-daily regimen after the haemodialysis session on dialysis days, to prevent the drug from being dialysed out.|
Antiretroviral therapy in patients with acute kidney injury
- In patients with acute kidney inury (AKI), NRTI dose adjustments should be implemented based on estimated CrCl calculation.
- TDF should be interrupted even if it is not thought to be the cause of the AKI.
- Re-challenge with TDF may be considered in patients 1 month post resolution of AKI if TDF was not the cause and renal function returns to normal.
- In patients with AKI who are not yet receiving ART, initiation is preferably deferred until AKI has resolved. But avoid significant delays.
- Once renal function is improving (creatinine is on a downward trend), standard NRTI doses should be reintroduced to avoid under-dosing.
In patients with AKI, NRTI dose adjustments should be implemented based on estimated CrCl calculation (see Table 25). TDF should be interrupted even if it is not thought to be the cause of the AKI. Care should be taken to identify other drugs which may affect renal function, such as aminoglycoside antibiotics, nonsteroidal anti-inflammatory drugs, co-trimoxazole and iodinated radiocontrast; these drugs should be avoided where possible, including temporary discontinuation.
Once there is clear evidence that renal function is improving (i.e. creatinine is on a downward trend), standard NRTI doses should be reintroduced to avoid under-dosing. In patients with AKI who are not yet receiving ART, initiation is preferably deferred until AKI has resolved. However, ART should not be delayed for longer than 2 weeks for this reason. If renal function does not show any improvement after treating an acute event (e.g. sepsis) and this persists beyond 3 months, then the patient should be assessed for chronic kidney disease and referred to a physician who can evaluate and investigate further.
|Common pitfall: Not performing NRTI dose adjustment in patients with AKI.|