Long-Term Immunologic and Virologic Responses in Patients with Highly Resistant HIV Infection Who Are Treated with an Incompletely Suppressive Antiretroviral Regimen

Abstract

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. Antiretroviral treatment-experienced HIV-infected patients with a genotype sensitivity score < or = 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 > or = 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. 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. 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.