Administration of trimethoprim/sulfamethoxazole 160/800 mg results in a 40% increase in lamivudine exposure, because of the trimethoprim component; the sulfamethoxazole component did not interact. However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole. When concomitant administration is warranted, patients should be monitored clinically. Co-administration of lamivudine with high doses of co-trimoxazole for the treatment of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis should be avoided. Coadministration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure (AUC) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. When possible, avoid chronic coadministration of Epivir with medicinal products containing sorbitol. Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.
Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

Lamivudine and trimethoprim/sulfamethoxazole (TMP/SMX) were coadministered to 14 HIV-positive patients in a single-centre, open-label, randomized, crossover study. Each patient received treatment with a single 300 mg dose of lamivudine and TMP/SMX 160/800 mg once a day for 5 days with concomitant administration of lamivudine 300 mg with the fifth dose in a crossover design. Coadministration of TMP/SMX with lamivudine resulted in an increase of 43±23% (mean ± SD) in lamivudine AUC, a decrease of 29±13% in lamivudine oral clearance, and a decrease of 30±36% in lamivudine renal clearance. The pharmacokinetic properties of TMP and SMX were not altered by coadministration with lamivudine. No change in dose of either drug is recommended. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP. Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine. Lamivudine and sorbitol solutions were coadministered to 16 healthy adult subjects in an open-label, randomized-sequence, 4-period, crossover trial. Each subject received a single 300-mg dose of lamivudine oral solution alone or coadministered with a single dose of 3.2 grams, 10.2 grams, or 13.4 grams of sorbitol in solution. Coadministration of lamivudine with sorbitol resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC(0-24), 14%, 32%, and 36% in the AUC(infinity), and 28%, 52%, and 55% in the Cmax; of lamivudine, respectively.
Epivir Prescribing Information, ViiV Healthcare, May 2019.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.
Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

Non-linear mixed effects modelling analysis on samples from 77 HIV-infected subjects receiving lamivudine alone (150 twice daily) or with nevirapine (200 mg twice daily) with concurrent trimethoprim/sulfamethoxazole (160/800 mg every other day [n=51], three times weekly [n=23], or twice daily [n=3]) revealed an effect of trimethoprim/sulfamethoxazole on lamivudine pharmacokinetics. There was a significant reduction of 31% in apparent oral clearance of lamivudine which would be expected to result in a 43% increase in the average steady-state concentration.
Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection. Sabo JP et al. AAPS Pharm Sci, 2002, 2: E1.

The effect of trimethoprim/sulfamethoxazole (160/800 mg once daily) on a single dose of lamivudine (300 mg) was studied in 14 HIV-infected subjects. Coadministration increased lamivudine AUV by 43% and decreased renal clearance by 35%. There was no effect of lamivudine on the pharmacokinetics of trimethoprim of sulfamethoxazole. Given the favourable safety profile of lamivudine, it is unlikely that this interaction will result in a significant increase in concentration-related toxicity at the doses studied.
Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole. Moore KHP, et al. Clin Pharmacol Ther, 1996, 59: 550-558.