Long-term effects of antiretroviral combination therapy on HIV type 1 DNA levels

HIV-1 RNA and DNA levels were measured in 58 patients, of whom 37 and 11, r espectively, received triple or double combination therapy. At baseline, st rong correlations were found between the number of HIV-1 DNA copies per 106 CD4(+) cells, the plasma HIV-1 RNA levels, and the isolation rate of HIV-1 from blood cells. In comparison with HIV-1 RNA, a much slower decline in H IV-1 DNA levels was seen, which probably represents a long lifetime of prov irus-bearing CD4(+) cells, In 10 untreated patients, the proviral load was stable. In patients receiving triple therapy, a significant decline in HIV- 1 DNA was seen independent of whether the proviral load was expressed as co pies per 10(6) CD4(+) cells or as copies per milliliter of blood. In contra st, a decline was seen only when the proviral load was expressed as copies per 106 CD4(+) cells in patients given two drugs. The difference between th e two patient categories is likely to be due to a more frequent infection o f CD4(+) cells during therapy in the patients with double therapy, Interpre tation of changes in HIV-1 DNA levels is thus dependent on how the proviral burden is expressed, Further studies should evaluate whether changes in HI V-1 DNA load can be used as markers of viral replication during efficient a ntiretroviral combination therapy.