Contribution of cellular HIV-1 DNA quantification to the efficacy analysis of antiretroviral therapy: a randomized comparison of 2 regimens, including 3 drugs from 2 or 3 classes (TRIANON, ANRS 081).
Cellular HIV-1 DNA level was sequentially measured by quantitative polymerase chain reaction in 141 patients not previously treated with highly active antiretroviral therapy (HAART), who were enrolled in a 72-week randomized trial (ANRS 081 "Trianon") comparing 2 regimens, including 3 drugs from 2 classes (indinavir + stavudine + lamivudine, group 1) or 3 classes (indinavir + stavudine + nevirapine, group 2). The median decrease from baseline to week 72 in cellular HIV-1 DNA level was not significantly different between the 2 groups (0.54 and 0.45 log10 copies/10 peripheral blood mononuclear cells [PBMCs] in groups 1 and 2, respectively), whereas a higher proportion of patients maintained a plasma HIV-1 RNA level less than 20 copies/mL at week 72 in group 1 than in group 2 (79% and 52%; P = 0.0009). Furthermore, the difference in cellular HIV-1 DNA decrease from baseline to week 72 between patients who achieved a plasma HIV-1 RNA level less than 20 copies/mL at week 72 and those who did not was not statistically significant (0.54 and 0.45 log10 copies/10 PBMCs, respectively; P = 0.14). The decay in cellular HIV-1 DNA from baseline to week 72 was higher in antiretroviral-naive patients than in pretreated patients (0.55 and 0.23 log10 copies/10 PBMCs, respectively; P = 0.0008). The cellular HIV-1 DNA level change under therapy was best fitted to a 2-phase decay model with a junction point at week 16, from which its half-life was estimated at 18 weeks during the initial phase and at 104 weeks thereafter. In conclusion, the changes under therapy in cellular HIV-1 DNA level, which were mostly coincident to those of plasma HIV-1 RNA, did not add significant information to the comparison of the viral efficacy of the 2 studied regimens.
Morand-Joubert
Laurence
L
Saint-Antoine Hospital, AP-HP, Université Paris VI, Paris, France. laurence.morand-joubert@sat.ap-hop-paris.fr
Marcellin
Fabienne
F
Launay
Odile
O
Guiramand-Hugon
Sonia
S
Gérard
Laurence
L
Yeni
Patrick
P
Aboulker
Jean-Pierre
JP
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D019469:Indinavir / Q000494:pharmacology / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine; D019469:Indinavir; D019829:Nevirapine; D018119:Stavudine