Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial.
BACKGROUND
The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients.


METHODS
A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n = 83) or lopinavir/ritonavir + zidovudine/lamivudine (n = 53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n = 83), and then focused on patients who had an HIV RNA < 50 copies/mL at week 48 (n = 56).


RESULTS
At week 96, 39 of 83 patients (47%) had HIV RNA < 50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA > 400 copies/mL. Focusing on the 56 patients with an HIV RNA < 50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA < 50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96.


CONCLUSIONS
By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA < 50 copies/mL at week 96. The occurrence in some patients of low-level viraemia (50-500 copies/mL) may increase the risk of drug resistance. First-line lopinavir/ritonavir monotherapy cannot be systematically recommended.
Ghosn
Jade
J
Department of Internal Medicine and Infectious Diseases, AP-HP, Bicêtre University Hospital, Le Kremlin-Bicêtre Cedex, France. jade.ghosn@bct.aphp.fr
Flandre
P
P
Cohen-Codar
I
I
Girard
P-M
PM
Chaix
M-L
ML
Raffi
F
F
Dellamonica
P
P
Ngovan
P
P
Norton
M
M
Delfraissy
J-F
JF
D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D057194:Intention to Treat Analysis; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D055118:Medication Adherence; D011744:Pyrimidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir