Background: Antiretroviral Therapy (ART) has significantly improved Human Immunodeficiency Virus (HIV) patients’ survival rates. However, the emergence of HIV Drug Resistance (HIVDR) has markedly reduced the effectiveness of Antiretroviral Therapy (ART).

Aim: This narrative review was conducted to review published studies on HIV drug resistance and its consequences.

Materials and methods: A literature search for this narrative review was carried out and the following databases were used PubMed, Google Scholar, and The Lancet. The cited articles were published from 1999 to 2021. The keywords used in the search of literature included ‘Antiretroviral therapy’, ‘resistance’, and ‘Human Immunodeficiency Virus drug resistance’, ‘HIV’, ‘HIV drug resistance’, ‘HIV vaccines’, and the Boolean word ‘AND’.

Results: There is a high prevalence of HIV drug resistance globally that has been associated with some factors such as older age, non-adherence to treatment, long treatment duration, lower cell count and high viral load. HIV drug resistance may lead to treatment failure, prolongation of the time required to achieve viral suppression and leads to increased mortality. Increasing access to viral load monitoring can help mitigate HIV drug resistance.

Conclusion: HIV drug resistance is a global threat to public health and has been associated with increased morbidity and mortality. Therefore, there is a need for more research to be carried out and various strategies like the use of antiretrovirals with a high genetic barrier to resistance need to be put in place to prevent further spread resistance. HIVDR must be monitored frequently taking into consideration the geographic variability. There is an urgent need for the development of anti-HIV vaccines that will help to prevent further transmission and spread of HIV.