Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

• Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs [ Time Frame: Basal, week 12, week 24 and week 48 ] [ Designated as safety issue: No ]
  

• Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL) [ Time Frame: Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: No ]
  
• Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls) [ Time Frame: Basal, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: No ]
  
• Lymphocyte activation marker CD8+HLADR+CD38+ [ Time Frame: Basal, week 2, week 4, week 12, week 24 and week 48. ] [ Designated as safety issue: No ]
  
• Raltegravir plasma trough concentration. [ Time Frame: Week 12, week 24 and week 48 ] [ Designated as safety issue: No ]
  
• Level of apoptosis in CD4 and CD8 T cells. [ Time Frame: Week 48 and week 60 ] [ Designated as safety issue: No ]
  

While highly active antiretroviral therapy (HAART) reduces plasma HIV-1 levels to below the limits of detection with standard assays, replication-competent virus persist in a stable, latent reservoir in resting CD4+ T cells. So, there is a rapid resumption in plasma viremia when therapy is interrupted.

In addition to cellular reservoir, other pharmacologically privileged areas such as the central nervous system and the genital tract might act as additional sources of residual virus in patients with undetectable levels of plasma HIV-1 RNA. There is great current interest in strategies for depleting and eliminating this reservoir.

The antiviral potency of current regimens emerges as an important determinant of complete viral control. In certain patients, the latent reservoir decay can be hastened with treatment intensification.

An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir. This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients being simplified to maintenance monotherapy with RAL or in the HIV-1 rebound kinetics and slope after a programmed treatment interruption.