HIV type 1 DNA development during long-term supervised therapy interruption.
We studied the pattern of HIV-1 DNA development and the association to other HIV-related factors during long-term supervised therapy interruption (LT-STI). Fifteen patients were treated with long-time protease inhibitor-based antiretroviral therapy (PI-ART). They had HIV-1 RNA at <50 copies/ml over 33.4 (SD 9.5) months and CD4(+) cell counts of 875 (SD 415) x 10(6)/liter. A real-time polymerase chain reaction, amplifying fragments of the HIV-1 pol gene and the human albumin gene simultaneously, was used to quantify HIV-1 DNA molecules in CD4(+) cells. The quantity of HIV-1 DNA in CD4(+) cells increased during LT-STI in all 15 patients, with an average doubling time of 2 months. Tentatively, three patterns were observed: rapid initial increase with subsequent stabilizing levels, rapid continuous increase, and slow increase. The HIV-1 DNA slope was positively related to the HIV-1 RNA maximum and steady state level and the baseline HIV-1 DNA value. It was inversely related to the decrease in CD4(+) cells both before the start of PI-ART and during the LT-STI. To conclude, HIV-1 DNA persists in infected CD4(+) cells despite long-term effective PI-ART and will increase after therapy interruption. The most important clinical predictor of long-term STI failure was the rapid CD4(+) cell decline before PI-ART. In patients with a steep pre-PI-ART slope it may be prudent to continue treatment and not initiate therapy interruption.
Eriksson
Lars E
LE
Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. Lars.Eriksson@omv.ki.se
Falk
Kerstin I
KI
Bratt
Göran A
GA
Leandersson
Ann-Charlotte
AC
Wahren
Britta
B
Leitner
Thomas
T
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors