Background:  Even though HAART can reduce plasma viremia to indetectable levels in most adherent patients, HIV cannot be eradicated. Integration of the viral genetic material into some long-life cells precludes this goal. Raltegravir (RAL) is the first of a new antiretroviral family which prevents HIV genome to integrate into host chromosomes. We hypothesize that throughout this mechanism it might produce a more pronounced decline in proviral DNA than other antiretroviral drugs, even after adjusting for viral response in plasma.

Methods:  Heavily antiretroviral-experienced patients with HIV resistant to at least the 3 classical antiretroviral drug classes initiated RAL along with an optimized background therapy. CD4 counts, plasma HIV RNA and proviral DNA in peripheral blood mononuclear cells (PBMC) were measured at baseline and at week 12 of treatment. A matched control group of multidrug-resistant patients who similarly begun a salvage regimen without RAL was evaluated.

Results:  Both groups had similar baseline demographic, clinical, and immuno-virologic characteristics; the genotypic sensitivity scores of HAART were not significantly different. The mean (SD) length of HIV infection was 14.8 (4.4) years, with no significant differences between groups. At week 12, there was a significant decline in plasma HIV RNA (p <0.0005) and CD4 gain (p <0.001) in both groups with respect to baseline, without significant differences between groups. However, proviral DNA load declined significantly only in the RAL arm.

Conclusions:  RAL may produce a significant decline in proviral DNA after 12 weeks of therapy, which is not seen with other antiretroviral drugs despite achievement of similar suppression of plasma viremia and CD4 gains. A higher potency of RAL over other antiretroviral drugs or its unique effect blocking HIV genome integration could explain this finding.