HIDRU has undertaken numerous clinical trials over the past 25 years (since 1996). The Unit has six established clinical research sites (CRSs) in the greater Durban area, which are approved by the Division of AIDS (DAIDS) and equipped to conduct large-scale clinical trials. Currently, the HIDRU conducts epidemiological, behavioural, basic science, and clinical research to investigate vulnerability to HIV and other infectious diseases as well as interventions (including vaccines and drugs) for prevention and treatment of these diseases.  All clinical research is conducted in partnership with stakeholders as part of the HIDRU community engagement programme which was established in the 90s.

In 2020, HIDRU partnered with CAPRISA and are part of the NIH funded  KwaZulu Natal Clinical Trials Unit (KZN CTU).

Historically, as the HIDRU was the only centre globally to test four out of five microbicide investigational products in five Phase III and three Phase II/IIb clinical trials. The excellent work produced by HIDRU gave the National Institutes of Health (NIH) the confidence to award HIDRU one of the largest grants, at three grant funding cycles, outside of the USA to undertake HIV prevention research.