A Research Study to See if a Change in Therapy for HIV Infection Can Improve the Immune Response to Treatment
Condition: HIV Infections
MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      Our goal is to determine if a change in therapy to one containing Kaletra can improve the
      immune response in patients who have previously been immune partial responders or
      non-responders. We also are interested in knowing if this agent improves immune response by
      affecting cluster of differentiation 4 (CD4) + T cell death (apoptosis) or by further
      inhibiting (preventing) ongoing, low-level, viral replication to levels below detection by
      current viral load measurements. This will help us understand why immune responses to
      effective antiretroviral therapy are so different and help determine some possible guidelines
      for managing patients with poor immune responses.

      Hypothesis: Patients with poor immune responses to HAART who receive Kaletra in place of
      their current PI or Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) while continuing
      their current 2 NRTI backbone will have improved immune response to therapy compared to
      patients who continue their current regimen.
    

Detailed description: 
      To our knowledge our study is the first study showing persistent apoptosis in a subgroup of
      patients with complete viral suppression in association with poor immune recovery. Immune
      alterations independent of active viral replication may be responsible. Recent data suggests
      that immune responses to antiretroviral therapy depend on residual or restored thymic
      function. Improved CD4+ counts in patients despite virologic treatment failure are associated
      with greater thymic function, while poor T cell responses despite suppression of HIV are seen
      with decreased thymic function. Discordant immune responses may also be due to differential
      effects of particular antiretroviral agents on T cell apoptosis independent of viral
      suppression. For example, protease inhibitors have been shown to decrease rates of apoptosis
      of uninfected T cells. Viral replication is never completely suppressed with HAART, even when
      patients have undetectable plasma HIV RNA. Therefore, varying degrees of low level viral
      replication or replication in certain cellular compartments may continue to drive T cell
      apoptosis. Finally, our data suggests that ex vivo rates of Peripheral blood mononuclear cell
      (PBMC) apoptosis could potentially be used predict immune recovery or identify subgroups of
      patients who may benefit most from changes in HAART or adjunctive immunomodulatory therapies.

      At this time, although there are excellent guidelines for how to evaluate and change therapy
      for patients with virologic failure, there are no recommendation and little data on
      approaches or strategies to change therapy for patients with poor immune responses. Kaletra
      (lopinavir/ritonavir) may be of benefit to patients with poor immune responses to HAART
      despite viral suppression. Kaletra may have greater potency and better suppression of viral
      replication that is below the level of detection by plasma polymerase chain reaction (PCR)
      for HIV-1 RNA. Kaletra also has an excellent pharmacokinetic profile which may result in
      superior inhibition of T cell apoptosis in vivo.
    

Intervention name(s): Kaletra + Current Dual NRTI Backbone; Current Regimen
Intervention type(s): Drug; Drug
Other intervention name(s): Lopinavir/ritonavir (LPV/r) + Current Dual NRTI Backbone; Current HIV treatment regimen
Intervention MeSH terms: Ritonavir; Lopinavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: HIV; HAART (Highly Active Anti-Retroviral Therapy) partial immune response; no immune response; Treatment Experienced