Decay of HIV-1 DNA in patients receiving suppressive antiretroviral therapy

We have examined the effect of potent antiretroviral regimens on the latent reservoirs of HIV-1. The HIV-1 DNA in the peripheral blood mononuclear cel ls (PBMC) of 10 patients with undetectable plasma HIV-1 RNA (<20 copies/ml) who had received combination antiretroviral therapy was assayed every 12 w eeks. No evidence of residual viral replication was found in the PBMC after 24 weeks of treatment. Although HIV-1 DNA remained detectable in all patie nts, it decreased significantly from 3.5 log copies/10(6) cells (range, 1.8 -4.7 log copies/10(6) cells) to 2.3 log copies/10(6) cells (range, 0.6-3.1 log copies/10(6) cells) after 60 weeks of suppressive therapy. Analysis bas ed on 6 patients who reached 60 weeks showed a slow decline with an estimat ed half-life of 40 weeks (range, 26-163 weeks). Genotypic analysis by seque ncing the HIV-1 pol gene revealed no changes in the reverse transcriptase o r protease coding regions after 48 to 60 weeks of therapy. The findings sug gest that, in addition to potent antiretroviral regimens, new strategies mu st be developed to ensure eradication of the latent reservoir of provirus, and hence of the virus itself.