Background: The persistence of latently infected CD4+ cells represents a major barrier to virus eradication in patients on combination antiviral therapy.  The half-life for decay of this latent pool of infected CD4+ T cells was estimated to be approximately 6 months in one study and 44 months in another.  In this study, we examined whether a new 4-drug combination might be more potent than common combination regimens in leading to a faster decay of the latent pool of infected cells.

Methods: PBMC samples were collected at baseline and every 3 months during therapy from 8 patients whose plasma viremia levels were suppressed to undetectable levels for at least 9 months while treated with lopinavir/ritonavir, efavirenz, tenofovir DF, and lamivudine.  HIV unspliced (US) mRNA and proviral DNA were quantified using a sensitive real-time PCR assay (5-30 copies/reaction).

Results:  A substantial reduction in cell-associated US mRNA was observed in all 8 subjects.  After 3 months of therapy, the median concentration of HIV US mRNA dropped sharply from 3.6 log copies/10⁶ PBMC at baseline to 2.1 log copies/10⁶ PBMC. At month 6 and thereafter, all subjects except one had undetectable US mRNA.  The decline in cell-associated US mRNA occurred concordantly with the reduction of plasma HIV RNA.  Similarly, the median concentration of proviral DNA dropped from 4.2 log copies/10⁶ PBMC at baseline to 3.7 and 3.4 log copies/10⁶ PBMC at months 3 and 9, respectively.  The rate of decline of US mRNA in this study appears to be faster than that observed previously with standard HAART (average decrease of 1.3 log copies/10⁶ PBMC after 16 months of treatment with less than 0.4 log copies/10⁶ PBMC decline in the first 10 months), although the decline rate of proviral DNA was similar to that previously observed. 

Conclusion: Initial results from this pilot study of a novel 4-drug antiretroviral regimen suggest that it may be possible to reduce the pool of latently infected CD4+ cells to a greater degree over a shorter period of time than that reported for other HAART treatment regimens.