We evaluated the HIV-1 reservoir in people with four-class drug-resistant (4DR) virus compared with those without drug resistance. Using the intact proviral DNA assay, we found that both groups had similar levels of intact HIV-1 DNA, suggesting that multidrug-resistant HIV does not significantly alter the size of the reservoir. These findings are a first step in studying the HIV-1 reservoir in the population with multidrug-resistant virus, and further studies are needed to confirm our results.