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. The gene discussed is CD4; the disease is metabolic disease.