Highly active antiretroviral therapy (HAART) reduces HIV-1 plasma viral load to undetectable levels in some patients, but the effects on latently infected CD4+ T cells and their role in HIV-1 persistence remain unclear. This study shows that 13 patients on HAART with undetectable plasma viremia had CD4+ T cells carrying integrated HIV-1 DNA and capable of producing infectious virus upon activation. Phenotypic analysis revealed syncytium-inducing virus in some patients, and unintegrated HIV-1 DNA was present in resting CD4+ T cells, suggesting ongoing viral replication. Despite HAART, HIV-1 DNA persists in latently infected CD4+ T cells, indicating a stable reservoir. The presence of unintegrated HIV-1 DNA in these cells suggests low-level viral replication. The study also found that replication-competent HIV-1 was present in resting CD4+ T cells of patients with undetectable plasma viremia, indicating that HAART does not fully eliminate the latent reservoir. These findings highlight the importance of measuring the size and replication competency of the latent reservoir to understand HIV-1 pathogenesis and assess HAART efficacy. The study used PCR and micrococulture assays to detect integrated and total HIV-1 DNA, as well as replication-competent virus. The results suggest that HIV-1 replication may continue in latently infected CD4+ T cells even when plasma viremia is undetectable. This has implications for the development of strategies to eradicate HIV-1.Highly active antiretroviral therapy (HAART) reduces HIV-1 plasma viral load to undetectable levels in some patients, but the effects on latently infected CD4+ T cells and their role in HIV-1 persistence remain unclear. This study shows that 13 patients on HAART with undetectable plasma viremia had CD4+ T cells carrying integrated HIV-1 DNA and capable of producing infectious virus upon activation. Phenotypic analysis revealed syncytium-inducing virus in some patients, and unintegrated HIV-1 DNA was present in resting CD4+ T cells, suggesting ongoing viral replication. Despite HAART, HIV-1 DNA persists in latently infected CD4+ T cells, indicating a stable reservoir. The presence of unintegrated HIV-1 DNA in these cells suggests low-level viral replication. The study also found that replication-competent HIV-1 was present in resting CD4+ T cells of patients with undetectable plasma viremia, indicating that HAART does not fully eliminate the latent reservoir. These findings highlight the importance of measuring the size and replication competency of the latent reservoir to understand HIV-1 pathogenesis and assess HAART efficacy. The study used PCR and micrococulture assays to detect integrated and total HIV-1 DNA, as well as replication-competent virus. The results suggest that HIV-1 replication may continue in latently infected CD4+ T cells even when plasma viremia is undetectable. This has implications for the development of strategies to eradicate HIV-1.