Correlates of antiviral immune restoration in acute and chronic HIV type 1 infection: sustained viral suppression and normalization of T cell subsets

AIDS Res Hum Retroviruses. 2002 Sep 20;18(14):999-1010. doi: 10.1089/08892220260235362.


Highly active antiretroviral therapy (HAART) has suppressed viral replication and facilitated normalization of T cell subsets, resulting in restoration of immunity against opportunistic pathogens. Induction of full immune restoration in chronically infected individuals, including HIV-specific helper T cell responses, is considered a priority, particularly if immunological control of HIV is to be achieved. Regimens containing dual protease inhibitors (PIs) have provided greater suppression of viremia than single-PI regimens. We therefore conducted a prospective analysis of factors associated with immune restoration after 3 years of therapy in two cohorts of acutely and chronically HIV-infected patients, comparing dual- versus single-PI regimens. Earlier and more durable returns of p24-specific proliferation were demonstrated in patients receiving dual-PI compared with single-PI regimens. Individuals with restored p24 responses had larger reductions in total HIV-specific cytotoxic T lymphocytes (CTLs) associated with stronger viral suppression, but Gag-specific CTLs remained higher, demonstrating that Gag-specific helper T cell responses were a critical component of functional immune restoration. On examination of clinical factors associated with immune restoration, we demonstrated that decreasing activation of CD8+ T cells (%CD8+ CD38+) and increasing proportions of CD4+ T cells were independently associated with restoration of p24 responses. Minimal immune activation, resulting from maximal suppression of viral replication, was required for long-term restoration and maintenance of Gag-specific T cell responses. This study uniquely demonstrates that dual-PI regimens are superior in achieving these levels of virological control and immune restoration in both chronic and acute infection, compared with single-PI or non-PI regimens.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • Chronic Disease
  • Gene Products, gag / immunology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV Long-Term Survivors
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation
  • T-Lymphocyte Subsets / immunology*
  • Time Factors
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / virology


  • Anti-HIV Agents
  • Gene Products, gag
  • HIV Protease Inhibitors