Background.Some treatment‐experienced patients with highly drug‐resistant human immunodeficiency virus (HIV) infection have no option but to continue to receive an incompletely suppressive regimen (ISR). We performed a study to determine their long‐term immunologic and virologic responses to ISR, to investigate risks for immunologic or virologic failure, and to examine for the occurrence of new drug‐resistance mutations.

Methods.Antiretroviral treatment–experienced HIV‐infected patients with a genotype sensitivity score 1, an HIV load >1000 copies/mL, and no available optimized regimen were included in the study. The proportion of patients treated with ISR who developed immunologic failure (defined as a 25% reduction in the CD4 cell count from the baseline level) and virologic failure (defined as a 0.5‐log₁₀ increase in the HIV load from the baseline level) was determined. Cox proportional hazards analysis was used to investigate variables associated with immunologic or virologic failure. New drug‐resistant mutations were calculated in 27 patients with sequential genotypes available.

Results.Forty‐seven patients (median duration of prior antiretroviral therapy, 89 months; median CD4 cell count, 277 cells/mm³; and median HIV load, 19,728 copies/mL) had multiple HIV mutations (a median of 5 nucleoside reverse‐transcriptase inhibitor mutations, 1 nonnucleoside reverse‐transcriptase inhibitor mutation, and 6 protease inhibitor mutations; median genotype sensitivity score, 0) at baseline. By 48 months after ISR use, 43% had developed immunologic failure, and 22% had developed virologic failure. None of the studied variables (i.e., age, <50 years; baseline HIV load, >100,000 copies/mL; baseline CD4 cell count, <200 cells/mm³; or inclusion of lamivudine in the treatment regimen) were associated with immunologic or virologic failure. New nucleoside reverse‐transcriptase inhibitor mutations occurred in 63% of patients, and new primary protease inhibitor mutations occurred in 52.6% of protease inhibitor recipients. No deaths occurred. A total of 8.5% of patients experienced a new AIDS‐defining event.

Conclusions.Most patients with highly drug‐resistant HIV infection who were treated with an ISR maintain durable immunologic and virologic responses. New drug‐resistant mutations occur frequently.