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 cells (PBMC) of 10 patients with undetectable plasma HIV-1 RNA (<20 copies/ml) who had received combination antiretroviral therapy was assayed every 12 weeks. No evidence of residual viral replication was found in the PBMC after 24 weeks of treatment. Although HIV-1 DNA remained detectable in all patients, 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 based on 6 patients who reached 60 weeks showed a slow decline with an estimated half-life of 40 weeks (range, 26-163 weeks). Genotypic analysis by sequencing the HIV-1 pol gene revealed no changes in the reverse transcriptase or protease coding regions after 48 to 60 weeks of therapy. The findings suggest that, in addition to potent antiretroviral regimens, new strategies must be developed to ensure eradication of the latent reservoir of provirus, and hence of the virus itself.
Izopet
J
J
Laboratoire de Virologie, Hôpital Purpan, Toulouse, France. izopet@cict.fr
Salama
G
G
Pasquier
C
C
Sandres
K
K
Marchou
B
B
Massip
P
P
Puel
J
J
D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015751:Genes, pol / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006207:Half-Life; D006801:Humans; D019469:Indinavir / Q000494:pharmacology / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000737:chemistry; D012189:Retrospective Studies; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D054303:HIV Reverse Transcriptase