Effect of persistent moderate viremia on disease progression during HIV therapy

J Acquir Immune Defic Syndr. 2004 Sep 1;37(1):1147-54. doi: 10.1097/01.qai.0000136738.24090.d0.


Objective: Although highly active antiretroviral therapy has been shown to lower plasma HIV-1 RNA in HIV infection, many patients do not reach the target goal of undetectable viremia. We evaluated whether risk of clinical progression varies by level of viral suppression achieved.

Design: Patients in the Collaborations in HIV Outcomes Research/United States cohort who maintained stable HIV-1 RNA levels of either <400, 400 to 20,000, or >20,000 copies/mL during a run-in period of at least 6 months were studied. Baseline was the first day after this period.

Methods: Proportional hazards models were used to quantify the relation between baseline HIV-1 RNA levels and risk of a new AIDS-defining diagnosis or death after adjusting for CD4 count, age, gender, ethnicity, study site, prior AIDS-defining diagnosis, and antiretroviral therapy history.

Results: Patients (N = 3010) were followed for up to 4.3 years after the 6-month run-in period, with 343 deaths or AIDS-defining diagnoses reported. The risk of a new AIDS-defining diagnosis or death was not significantly different in the 400 to 20,000- and <400-copies/mL groups (6% vs. 7%, hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 0.7-1.4; P = 0.9) but was significantly higher in the >20,000-copies/mL group (26%, HR = 3.3, 95% CI: 2.5-4.4; P < 0.001 vs. the <400-copies/mL group). Median CD4 count changes during the first year of follow-up showed increases of 75 and 13 cells/mm for the <400- and 400 to 20,000-copies/mL groups, respectively, whereas the >20,000-copies/mL group had a decrease of 23 cells/mm.

Conclusions: Patients who maintained baseline HIV-1 RNA levels of 400 to 20,000 copies/mL for at least 6 months preserved immunologic status and were no more likely to die or develop a new AIDS-defining diagnosis in the time frame studied than those with baseline levels <400 copies/mL. Patients with HIV-1 RNA levels >20,000 copies/mL at baseline had greater clinical and immunologic deterioration. These data suggest that maintenance of moderate viremia may confer clinical benefit not seen when viremia exceeds 20,000 copies/mL, and this should be taken into account when considering the risks and benefits of continuing failing therapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • HIV Infections / diagnosis*
  • HIV Infections / drug therapy
  • HIV Infections / mortality*
  • HIV Infections / physiopathology
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Male
  • Proportional Hazards Models
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • United States
  • Viral Load
  • Viremia / virology*


  • Anti-HIV Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors