The long-term feasibility of a drug conservation strategy that allows low-level viral replication is unknown. We performed a retrospective study of treated HIV-infected patients with stable detectable viral replication (<10,000 copies/mL [low-level viremia]) and compared their clinical, virologic and immunologic courses with those of treated patients with undetectable viremia and viremia (≥10,000 copies/mL [high-level viremia]). Viral reverse transcriptase and protease genotype and HIV-specific CD4 T-cell responses were determined using patient-derived samples. Clinical and immunologic benefits were maintained in patients with partial virologic suppression (≤10,000 copies/mL). Although low-level viral replication under drug pressure led to the accumulation of resistance mutations in most subjects' viruses, most subjects retained susceptibility to drugs in ≥2 classes of antiretroviral medications. HIV-specific CD4+ T-cell immunity was detected in most subjects with low-level and undetectable viremia and may have a role in controlling viremia in the setting of partial suppression.