Dynamics of cellular HIV-1 DNA levels over 144 weeks of darunavir/ritonavir monotherapy versus triple therapy in the MONET trial.
BACKGROUND
In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized.


METHODS
In MONET, patients on stable combination ART for at least 6 months with plasma HIV-1 RNA <50 copies/mL and no history of virologic failure switched to DRV/r 800/100 mg once daily, either alone (n = 127) or with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (n = 129). In a representative subset of 146 patients, total HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) was tested retrospectively at baseline, week 48, week 96, and week 144.


RESULTS
Mean HIV-1 DNA levels at baseline vs week 144 were 2.50 vs 2.49 log10 copies/106 PBMC in the monotherapy arm and 2.59 vs 2.61 log10 copies/106 PBMC in the triple therapy arm, with mean (median) changes of -0.05 (-0.03) and +0.03 (+0.01) log10 copies/106 PBMC in the 2 arms, respectively. Overall baseline HIV-1 DNA levels were higher in patients with nadir CD4 counts <200 cell/µL (P<.05) and in patients who over 144 weeks experienced at least 1 HIV-1 RNA measurement >50 copies/mL (P < .05).


CONCLUSIONS
In this substudy of the MONET trial, HIV-1 DNA levels remained stable during 144 weeks of either DRV/r monotherapy or triple therapy with DRV/r + 2 NRTIs. In both treatment arms, baseline HIV-1 DNA levels were predicted by the nadir CD4 cell count and predictive of plasma HIV-1 RNA detection during follow-up.
University of Liverpool, UK.
Anna Maria
AM
Geretti
Jose R
JR
Arribas
Erkki
E
Lathouwers
Geraldine M
GM
Foster
Rabia
R
Yakoob
Sabine
S
Kinloch
Andrew
A
Hill
Yvon
Y
van Delft
Christiane
C
Moecklinghoff
D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D000069454:Darunavir; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir