Background:  Physiological changes in pregnancy may alter drug handling and predispose to virological failure if levels are too low. This study sought to examine the efficacy of lopinavir (LPV) when initiated at standard dosing as part of HAART in pregnancy.

Methods:  From the ongoing cohort of pregnancies in HIV-1-infected women those who initiated lopinavir/ritonavir (LPV/r) (3 twice-daily) as part of HAART in pregnancy were selected. Trough LPV levels were taken at steady state in the third trimester.

Results:  From April 2004 to September 2005, 16 women initiated LPV/r in pregnancy and had trough levels performed in the third trimester; 14(88%) were black African and all of these were HIV non-B subtype. In the index pregnancy, 2 women had initiated a different regimen; 1 switched from nelfinavir to LPV/r because of diarrhea and 1 failed on nevirapine with the K103N mutation. None were on other medications known to interfere with LPV/r pharmacokinetics. Resistance testing prior to LPV/r initiation did not demonstrate any relevant protease inhibitor (PI) or nucleoside reverse transcriptase inhibitor (NRTI) mutations. Median gestation at LPV/r initiation = 25 weeks (range 14 to 31). NRTI backbone was zidovudine/lamivudine (ZDV/3TC) in 14 (88%) and tenofovir (TDF)/3TC in 2 (12%). Median pre-treatment CD4 and HIV viral load = 328 x 10⁶/L (147 to 846) and 4753 copies/mL (49 to 43,743). Median time from LPV initiation to trough sampling was 70 days (16 to 147). Median time from last dose to trough sampling was 13 hours (11 to 15).The median trough LPV level in the third trimester (median gestation at sampling 34 weeks) was 3660 ng/mL (249 to 5655); 15 (94%) had trough levels above the minimum trough required to inhibit wild type HIV (1000 ng/mL); 14 (88%) had an undetectable viral load at that time and adherence issues were identified in the other 2 (viral load 116 and 523 copies/mL). All of the infants (now 3 months of age) are HIV PCR negative (n = 9).

Conclusions:  In this cohort, the majority achieved adequate LPV plasma levels (94%) and virological suppression (88%) at standard dosing. This supports the use of LPV/r at standard dosing in pregnancy with therapeutic drug monitoring without automatic recourse to 4 twice-daily as previously suggested.