title: Long-term immunologic and virologic responses in patients with highly resistant HIV infection who are treated with an incompletely suppressive antiretroviral regimen.
abstract: 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 < 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.
  
  
  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.
authors: University of Michigan Health System, Ann Arbor, MI 48109-5378, USA.
authors: Tejal
authors: T
authors: Gandhi
authors: Vijayalakshmi
authors: V
authors: Nagappan
authors: Sandro
authors: S
authors: Cinti
authors: Wei
authors: W
authors: Wei
authors: Powel
authors: P
authors: Kazanjian
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D012367:RNA, Viral