No abstract

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard-and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)

In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.

Objectives Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. Methods This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2–6 mg plus spironolactone 100–300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30–48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants. Results No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01–1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2–65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70–57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study. Conclusions Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.

Rifampicin reduces plasma concentration of most HIV protease inhibitors. Lopinavir boosted with ritonavir (LPV/r) could be an option to treat TB-HIV patients. Our aim was to evaluate lopinavir interaction with rifampicin during TB-HIV therapy. TB-HIV patients who could not use efavirenz and with no genotypic resistance to lopinavir were included. Rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 2000 mg were started at day one for 6 months and LPV/r plus two nucleoside/nucleotide reverse transcriptase inhibitors were introduced at day 30. LPV/r dose was started at 400/100 mg BID and escalated over 7 days to 800/200 mg BID. Pharmacokinetic sampling was performed at day 15 (rifampicin), 45, 90, 180 (rifampicin, lopinavir, ritonavir) and 210 (lopinavir, ritonavir). Viral load (VL) and CD4 counts were performed at baseline and days 30, 60, 120, and 180. Genotypic testing was done in baseline and in the last visit. Fifteen patients were enrolled. Five were excluded during exclusively TB therapy. After LPV/r introduction five patients were excluded, three due to adverse events, and two due to low adherence. Five patients finished the study, two of them with VL<50 copies/mL. LPV/r genotypic resistance was detected in one patient. Lopinavir concentrations were below 1 µg/mL in 4/10 patients (in one study point), and one in two study points. Lopinavir concentrations were above 4 µg/mL in 6/10 patients, at least in one pharmacokinetic sample. Although target drug concentrations of lopinavir were achieved for most patients, adverse events were frequent and low adherence was observed for both TB and HIV therapies, showing how difficult it is to treat both diseases simultaneously. Hepatic and pancreatic enzymes should be routinely monitored. J o ur nal o f A ID S & Cli n ic a l R es earc h