Coadministration decreased plasma concentrations of methadone. Monitoring plasma concentrations of methadone is recommended.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration of methadone (5 mg single dose) and lopinavir/ritonavir (400/100 mg twice daily for 10 days) to 11 HIV- subjects resulted in a 45% decrease in methadone Cmax and a 53% decrease in AUC. Dosage of methadone may need to be increased when coadministered with Kaletra.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Lopinavir/ritonavir (400/100 mg twice daily) was commenced in 18 HIV+ patients participating in a methadone maintenance program. Median (range) methadone dose at study entry was 95 (40-130) mg/day. None of the patients experienced symptoms of opioid withdrawal, no patients requested a change in methadone dosing and there was no indication for the prescribing physician to adjust methadone dosing based on daily clinical assessment during the 28 day evaluation period after starting lopinavir/ritonavir.
Lack of methadone dose alterations or withdrawal symptoms during therapy with lopinavir/ritonavir. Stevens RC, Rapaport S, Maroldo-Connelly L, et al. JAIDS, 2004, 33: 650-651.

The effect of lopinavir/ritonavir (400/100 mg twice daily) and ritonavir alone (100 mg twice daily) on methadone was studied in 15 HIV- methadone-maintained subjects. When compared to values obtained for methadone alone, decreases in methadone Cmin, AUC and Cmax of 26, 28 and 26% respectively were observed with lopinavir/ritonavir. There was a significant increase in opiate withdrawal symptoms, the incidence of which was related to the magnitude of decrease in methadone Cmin (12% decrease – no change in withdrawal symptoms; 32% decrease – moderate increase in symptoms; 42% decrease – severe increase in symptoms). In contrast, coadministration of ritonavir produced a modest but not significant increase in methadone concentrations, and there were no increases in opiate withdrawal symptoms.
The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients. McCance-Katz EF, Rainey PM, Friedland G, Jatlow P. Clin Infect Dis, 2003, 37: 476-482.

Methadone-stabilised (n=15) or volunteer (n=15) subjects received lopinavir/ritonavir (400/100 mg twice daily) or ritonavir alone (100 mg twice daily) for 7 days. Ritonavir AUC was increased by ~60% when coadministered with methadone (6.5 vs 11.0 mg/ml.h), but when the same dose was administered in combination with lopinavir, no significant changes in ritonavir exposure were observed (8.7 vs 7.7 mg/ml.h). Methadone did not appear to alter the pharmacokinetics of lopinavir (AUC 84.7 vs 86.3 mg/ml.h; Cmin 4.4 vs 4.6 mg/L; Cmax 10.0 vs 9.3 mg/L; alone vs with methadone).
Smith P, McCance-Katz E, Sarlo J, et al. Methadone increases ritonavir exposure when administered alone but not with lopinavir/ritonavir combination. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September, 2003, abstract H-2000.

Methadone was coadministered with lopinavir and the plasma levels of methadone were obtained in 8 HIV + patients. It was shown that methadone AUC was decreased by 36% and mean Cmax by 44%. None of the patients experienced symptoms of methadone withdrawal and no dose adjustment for methadone was needed.
Absence of opioid withdrawal symptoms in patients receiving methadone and the protease inhibitor lopinavir-ritonavir. Clarke S, Mulcahy F, Bergin C, et al. Clin Infect Dis, 2002, 34: 1143-1145.