CD4 and HIV infectious disease: Patients with pre-existing kidney disease or with risk factors for TDF-associated renal impairment, such as cardiovascular or metabolic diseases, concomitant nephrotoxic medications, low body weight, advanced age and lower CD4 cell count are typically under-represented in clinical trials.[22] There is an issue with this as patients in trials are different from those seen in clinical practice, who are aging populations, with advanced HIV infections and multiple comorbidities.