Objective: To describe a case of exacerbated mania potentially related to an interaction between lopinavir/ritonavir and valproic acid (VPA) and propose a mechanism of action for this interaction. Case Summary: A 30-year-old man with bipolar disorder and HIV initiated treatment with lopinavir/ritonavir, zidovudine, and lamivudine. Prior to beginning therapy with these antiretrovirals, he was receiving VPA 250 mg 3 times daily, with his most recent VPA concentration measured at 495 μmol/L. Twenty-one days after starting antiretroviral treatment, he became increasingly manic. His VPA concentration at admission was 238 μmol/L, a 48% decrease. The daily VPA dose was increased to 1500 mg, and olanzapine was introduced. The VPA concentration following this dose escalation was 392 μmol/L, and the patient improved clinically. Discussion: Fifty percent of VPA is metabolized by glucuronidation, 40% undergoes mitochondrial β-oxidation, and less than 10% is eliminated by the cytochrome P450 isoenzymes. Ritonavir can induce glucuronidation of several medications including ethinyl estradiol, levothyroxine, and lamotrigine. We believe that ritonavir-mediated induction of VPA glucuronidation resulted in a decrease in VPA concentrations and efficacy. An objective causality assessment suggested that the increased mania was probably related to the decrease in VPA concentration and that a possible interaction exists between lopinavir/ritonavir and VPA. Conclusions: A potential interaction exists between VPA and all ritonavir-boosted antiretroviral regimens. Clinicians should monitor patients closely for a decreased VPA effect when these medications are given concomitantly.

Background: Migrants represent an increasing proportion of people living with HIV in many developed countries. We aimed to describe the HIV care cascade and baseline genotypic resistance for newly diagnosed asylum seekers referred to the McGill University Health Centre (MUHC) in Montreal, Quebec, Canada. Methods: We conducted a retrospective cohort study of patients linked to the MUHC from June 1, 2017 to October 31, 2018. We calculated the median time (days; interquartile range (IQR)) from: 1) entry into Canada to immigration medical examination (IME) (i.e. HIV screening); 2) IME to patient notification of diagnosis; 3) notification to linkage to HIV care (defined as a CD4 or viral load (VL) measure); 4) linkage to HIV care to combination antiretroviral therapy (cART) prescription; and 5) cART prescription to viral suppression (defined as a VL < 20 copies/mL). We reviewed baseline genotypes and interpreted mutations using the Stanford University HIV Drug Resistance Database. We calculated the proportion with full resistance to > 1 antiretroviral. Results: Overall, 43% (60/139) of asylum seekers were newly diagnosed in Canada. Among these, 62% were late presenters (CD4 < 350 cells/μl), 22% presented with advanced HIV (CD4 < 200 cells/μl), and 25% with high-level viremia (VL > 100,000 copies/ml). Median time from entry to IME: 27 days [IQR:13;55]; IME to notification: 28 days [IQR:21;49]; notification to linkage: 6 days [IQR:2;19]; linkage to cART prescription: 11 days [IQR:6;17]; and cART to viral suppression: 42 days [IQR:31;88]; 45% were linked to HIV care within 30 days. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. Conclusions: While the majority of newly diagnosed asylum seekers were late presenters, only 45% were linked to care within 30 days. Once linked, care and viral suppression were rapid. Delays in screening and linkage to care present increased risk for onward transmission, and in the context of 21% baseline resistance, consideration of point-of-care testing and immediate referral at IME screening should be made.

Background: Like other chronic viral illnesses, HIV infection necessitates consistent self-management and adherence to care and treatment, which in turn relies on optimal collaboration between patients and healthcare professionals (HCPs), including physicians, nurses, pharmacists, and clinical care coordinators. By providing people living with HIV (PLHIV) with access to their personal health information, educational material, and a communication channel with HCPs, a tailored patient portal could support their engagement in care. Our team intends to implement a patient portal in HIV-specialized clinics in Canada and France. We sought to understand the perceived risks and benefits among PLHIV and HCPs of patient portal use in HIV clinical care. Methods: This qualitative study recruited PLHIV and HIV-specialized HCPs, through maximum variation sampling and purposeful sampling, respectively. Semi-structured focus group discussions (FGDs) were held separately with PLHIV and HCPs between August 2019 and January 2020. FGDs were recorded, transcribed, coded using NVivo 12 software, and analyzed using content analysis. Results: A total of twenty-eight PLHIV participated in four FGDs, and thirty-one HCPs participated in six FGDs. PLHIV included eighteen men, nine women, and one person identifying as other; while, HCPs included ten men, twenty women, and one person identifying as other. A multi-disciplinary team of HCPs were included, involving physicians, nurses, pharmacists, social workers, and clinical coordinators. Participants identified five potential risks: (1) breach of confidentiality, (2) stress or uncertainty, (3) contribution to the digital divide, (4) dehumanization of care, and (5) increase in HCPs’ workload. They also highlighted four main benefits of using a patient portal: (1) improvement in HIV self-management, (2) facilitation of patient visits, (3) responsiveness to patient preferences, and (4) fulfillment of current or evolving patient needs. Conclusion: PLHIV and HCPs identified both risks and benefits of using a patient portal in HIV care. By engaging stakeholders and understanding their perspectives, the configuration of a patient portal can be optimized for end-users and concerns may be mitigated during its implementation.

β-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that β-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of β-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of β-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC_{0–12 h}), maximum (C_max) and minimum (C_min) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC_{0–12 h} and C_min (−10%, +4%) after β-carotene supplementation. The M8 C_min was increased by 31% while the M8 AUC_{0–12 h} and C_max were unchanged. During the 28 day period, mean CD4⁺ % and CD4⁺:CD8⁺ ratio increased significantly (p < 0.01). β-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure.

Background: It is recommended to boost atazanavir with ritonavir (ATV/r) when it is combined with tenofovir disoproxil fumarate (TDF) because of drug interactions. For tolerability, unboosted atazanavir (ATV) is sometimes coadministered with TDF. The objective of this study was to evaluate the impact of this interaction on the proportion of patients achieving target ATV C_troughs and genotypic inhibitory quotients (GIQ). Materials and Methods: A therapeutic drug monitoring database was screened to evaluate ATV concentrations. Differences in C_trough and GIQ values among 4 antiretroviral drug combinations were evaluated. Results: Three hundred eight C_troughs, 91 GIQs, and 92 viral loads were evaluated for 238, 68, and 69 patients, respectively. Patients receiving ATV/r and TDF compared with ATV and TDF were more likely to have a therapeutic C_trough (odds ratio, 2.27; 95% confidence interval: 1.46–3.52; P < 0.001). Among patients on unboosted ATV, the odds of having a therapeutic ATV C_trough did not differ between groups with TDF versus without TDF. Although ritonavir increased the GIQ in patients receiving TDF (odds ratio, 3.38; 95% confidence interval: 1.30–8.81; P = 0.013), a similar proportion of patients on TDF and either ATV/r or ATV achieved a therapeutic GIQ. Conclusions: In patients receiving TDF, ritonavir increased the ATV C_trough and GIQ and patients on ATV/r were more likely to have therapeutic C_troughs. However, among subjects without ritonavir boosting, TDF compared with other nucleosides did not influence the odds of achieving a therapeutic ATV C_trough. These data suggest that ritonavir boosting of ATV is prudent, particularly in patients with resistance mutations.