Introduction Human immunodeficiency virus (HIV) is a double stranded RNA retrovirus. According to the World Health Organization more than 30 million individuals were estimated to have HIV by the end of 2020, about 60% of which are in the African region. Pre-treatment drug resistance (PDR) can be defined as the resistant virus strains transmitted at the time of infection or acquired during previous exposure to ARV. This study asses the effect of drivers in PDR. Method: This study was conducted with data extracted from published, publicly available data bases and reports by international organizations. The main sources were United Nation data bases and published reports from World Health Organization.  Inferential statistics were used to assess the PDR to anti-retroviral drugs. A linear regression model was used to investigate the association between PDR and previous exposure to anti-retrovirals and anti-retroviral therapy, pre-exposure prophylaxis, national health expenditure, human development index, and drug stock-out for different classes of anti-retroviral drugs.   Results: The result indicated that NNRTI drug resistance was most common, and seven out of 29 countries had PDR to all four drug classes. The human development index was positively associated with INSTI and PI PDR (p<0.05), while NNRTI and NRTI were mainly positively associated with previous exposure to anti-retrovirals. Conclusion: This study assessed the impact of socio-economics determinants (human development index and national health expenditure), drug logistic determinants (stock-out), and patients’ determinants (adherence and previous exposure to any kind of anti-retrovirals) on PDR. For expensive drug classes (PI and INSTI) the resistance was positively associated with human development index. Previous exposure to anti-retrovirals was associated with increased resistance in NNRTI and NRTI.