Introduction: Zimbabwe, like other resource limited countries, manages HIV infection using the public health approach with standard antiretroviral therapy (ART) regimens for first, second and third-line treatment. Third-line ART is the last available treatment option and is based on dolutegravir and darunavir use after HIV drug resistance testing. Patient Presentation: We report here a 17-year-old patient on dolutegravir (DTG) and Darunavir based third-line antiretroviral therapy (ART) previously exposed to raltegravir who develops multidrug resistance HIV to the four ART classes available in Zimbabwe. Management and Outcome: A trophism assay revealed that patient has CXCR4 trophic virus and hence will not benefit from Maraviroc. Patient is currently stable and receiving a holding regimen of abacavir, lamivudine and lamivudine. Conclusion: This is the first documented case of multiclass resistance to the four available ART classes in Zimbabwe. The development and transmission of multiclass HIV drug resistance in resource limited settings has potential to undo the gains of national ART programs. There is need to ensure optimum adherence to ART even in the era of DTG.