Note: In the 2021 WHO consolidated HIV guidelines (1), baseline measurement of creatinine is not required before initiating ART for people living with HIV with the preferred tenofovir-based regimen. a Factors associated with a higher risk of renal dysfunction include: decompensated cirrhosis, CrCl <50 mL/min, older age >60 years, body mass index (BMI) <18.5 kg/m2 (or body weight <50 kg), poorly controlled hypertension, proteinuria, uncontrolled diabetes, active glomerulonephritis, concomitant use of nephrotoxic drugs or a boosted protease inhibitor for HIV and solid organ transplantation. b Measurement of baseline renal function includes: serum creatinine levels and calculation of CrCl/estimated glomerular filtration rate (eGFR) using the MDRD formula. MDRD formula: eGFR = 175 × (serum Cr)-1.154 × (age)-0.203 × 1.212 if the person is Black) × 0.742 (if the person is female). Assessing and monitoring renal function

• 1.For people initiating treatment with an estimated CrCl or glomerular filtration rate (eGFR) <50 mL/min or with risk factors for renal dysfunction, including older age, long-term diabetes, uncontrolled hypertension or severe osteopaenia or osteoporosis, consider either using ETV instead or avoiding TDF or reducing the dose of TDF (guided by Table 17.1).
• 2.Use of TDF should be avoided with concurrent nephrotoxic drugs (such as aminoglycosides, amphotericin B, foscarnet, ganciclovir, vancomycin and cidofovir) because of the increased risk of reducing renal function.
• 3.Monitoring renal function during nucleos(t)ide analogue therapy may include: urine dipsticks for proteinuria and glycosuria (in the absence of diabetes or if blood glucose is well controlled), serum creatinine, estimated eGFR decline, serum phosphate, urine proteinto-creatinine ratio (or fractional excretion of phosphate, if available) as well as growth of children receiving TDF. For individuals with normal renal function, a minimum monitoring package could include annual urine dipstick testing and creatinine measurement for eGFR if possible.
• 4.The frequency of renal monitoring during nucleos(t)ide analogue therapy depends on the presence of risk factors for renal dysfunction and should be more frequent among people at higher risk. a. People at high risk of renal toxicity: every six months unless there is evidence of worsening. Closer renal monitoring is advisable among people with CrCl <50 mL/min. b. People at low risk of renal toxicity: either no routine monitoring of renal function or every 12 months unless there is evidence of worsening.
• 5.During treatment, if the CrCl falls below 50 ml/min or in case of progressive decline of renal function, consider adjusting the dosing interval of TDF or switching to ETV or TAF (guided by Table 17.1) and closely monitoring renal function.
• 6.If low bone mineral density is detected or suspected because of a fracture, then appropriate consultation should be obtained, with a switch from TDF to ETV or TAF. • Known risk factors for developing TDF-induced nephrotoxicity include underlying renal dysfunction, low CD4 count, low body weight and comorbid hypertension, diabetes, HIVassociated kidney disease, HIV or C coinfection and TDF in combination with a ritonavirboosted protease inhibitor in people with HIV infection (10–12). Managing these comorbid conditions should be given priority.

• People receiving TAF should be monitored for weight gain and lipid rises as well as metabolic syndrome.
• Age and advanced liver disease are additional contributing factors that can help identify those at greatest risk of osteoporotic fracture. Dual-energy X-ray absorptiometry can be used to monitor bone mineral density changes for people receiving TDF. The frequency of monitoring will depend on each person’s age and health status. The accuracy of the Fracture Risk Assessment Tool (as an alternative to dual-energy X-ray absorptiometry) has also been evaluated (53). TDF-containing regimens may be replaced with non-TDF-containing regimens for those at higher risk of fragility fracture.