Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease

Lancet. 1998 Jun 6;351(9117):1682-6. doi: 10.1016/s0140-6736(97)10291-4.


Background: Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included.

Methods: 20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders.

Findings: Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells.

Interpretation: HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antibodies, Monoclonal
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Division
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1* / genetics
  • Humans
  • Immunocompetence
  • Indinavir / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Protease Inhibitors / therapeutic use
  • RNA, Viral / analysis
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / therapeutic use
  • Time Factors
  • Viral Load*


  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Indinavir
  • Ritonavir