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Objectives: The management of psychiatric illness in HIV-infected patients is clinically challenging because of the risk of potential drug–drug interactions. Here, we aimed to measure the antidepressant and/or antipsychotic drug concentrations in HIV-infected patients during routine outpatient visits. Methods: Six hundred HIV-infected patients were screened during the first 15 months after the introduction of our outpatient polytherapy management service in a search for subjects treated with psychotropic drugs for at least 3 months. The distribution of psychotropic drug concentrations in HIV-infected patients was compared with that observed in a control group of HIV-negative patients monitored over the same period. Results: The search identified 82 HIV-infected patients concomitantly receiving antiretroviral and psychotropic drug treatment, 55% of whom had plasma psychotropic drug concentrations that were below minimum effective levels. The same result was found in only 26% of the samples taken from HIV-negative patients. These results were not affected by patients' gender, age, adherence to therapies or drug–drug interactions. Conclusions: A higher rate of sub-therapeutic antidepressant and/or antipsychotic drugs concentrations were found in HIV-infected patients. The creation of multidiscliplinary specialist teams may contribute to improving the management of such complex patients. [ABSTRACT FROM AUTHOR]

The treatment of hepatitis C virus in monoinfected and HIV-coinfected patients has greatly changed over recent years as a result of the introduction of direct-acting antiviral agents (DAAs), which have revolutionized clinical outcomes and led to sustained virological response rates above 90-95%. The discovery of new molecules and the subsequent competition between pharmaceutical companies, together with the negotiated price policies pursued by many national health systems, have led to a gradual reduction in the cost of DAAs, and expand their use to an increasing number of patients, including those with mild liver damage. However, the cost of branded DAAs is still too high for many developing countries, and many patients are still left without therapy. In this context, the availability of generic DAAs certainly provides a major opportunity for further cost savings in industrialized countries and will ensure broader access to treatment elsewhere. However, their more widespread use must not lead to a reduction in pharmaceutical quality because this could result in serious clinical consequences, including high rat failures, and selection of drug resistance. It is therefore essential that all generic formulations of DAAs are pre-qualifi ed by the World Health Organization, and that real-life studies are carried out to verify their pharmacokinetic bioequivalence (ideally in patients, and not just in healthy volunteers) and clinical effectiveness. In this regard, lessons from expanding access programs in the HIV fi eld would be very helpful. [ABSTRACT FROM AUTHOR]

Background: Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)-experienced people living with HIV (PLWH)., Setting: Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH., Methods: The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit. Virologic, biometric, and metabolic parameters were evaluated at baseline (T0) and at 1-3 (T1), 6 (T2), and 12 (T3) months. Univariate and multivariate survival analyses assessed the 28-week probability of persistence on the regimens. Patient satisfaction was measured using the HIV Treatment Satisfaction Questionnaire., Results: Ninety-five PLWH were included, 52 in DOR + RAL and 43 in DOR + DTG. Six treatment discontinuations were reported during a mean of 37 (±17) weeks of FU (incidence of 2.7 × 1000 person-weeks FU). Only 2 were the result of virological failure without resistance mutations. DOR + DTG demonstrated significantly higher 28-week persistence than DOR + RAL (HR 1.90, 95% CI: 1.24-2.90, log-rank: P = 0.003). Weight, waist circumference, and fasting lipids reduced considerably at T3 vs T0. Overall, high satisfaction with the new treatment was reported, particularly in the DOR + RAL (68 (64-72)/72), compared with the DOR + DTG group (58 (50-65)/72, P < 0.001)., Conclusions: Our experience revealed few treatment discontinuations, improved metabolic parameters, and high patient satisfaction among ART-experienced PLWH switching to DOR combined with INI, irrespective of the specific INI used., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting., Methods: HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons., Results: Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation., Conclusions: Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.

Objective: In a setting of free access to HIV care, we compared the early treatment outcomes of HIV-infected undocumented migrants (UMs), documented migrants (DMs), and Italian subjects., Methods: The clinical data of 640 Italians and 245 migrants who started combined antiretroviral therapy (cART) at an HIV clinic in Milan, Italy, were reviewed. The migrants were mainly Latin Americans (83 DMs and 56 UMs) or sub-Saharan Africans (52 DMs and 11 UMs), but a minority were of other origin (33 DMs and 10 UMs). Retention in follow-up and HIV suppression were compared between UMs, DMs, and natives 12 months ± 90 days after start of cART., Results: There were no significant between-group differences in the stage of HIV infection at the start of cART or the type of regimen received. The Latin American DMs and UMs included a higher proportion of transgender women than the other ethnic groups (P < 0.001). The UMs were less frequently followed up after 12 months than the DMs and natives (P = 0.004) and were more frequently permanently lost to follow-up (P < 0.001). UM status was an independent predictor of lost to follow-up (adjusted odds ratio 8.05, P < 0.001). The DMs and UMs were less frequently HIV suppressed after 12 months than the natives (78% and 80.7% vs 90.5%, P = 0.001), and Latin American migrants were significantly less likely to be virologically suppressed than the natives (adjusted odds ratio 0.30, P = 0.001)., Conclusions: Despite their free access to cART, subgroups of migrants facing multiple levels of vulnerability still have difficulties in gaining optimal HIV care.

Background: Severe thrombocytopenia (TCP, platelets <50 × 10⁹/L) is relatively frequent during HIV infection and is associated with bleeding risk and disease progression. We investigated the changes in the incidence of severe TCP and its predisposing conditions in a cohort of HIV-positive subjects., Methods: The incidence and predictors of platelet counts <50 × 10⁹/L were investigated in all patients enrolled at our institution between 1985 and 2012. Three different periods were considered on the basis of the available antiretroviral regimens: P1 (1985-1989), P2 (1990-1996), and P3 (1997-2012). Incidence rates were assessed using Poisson regression models and the predictors by means of Cox regression., Results: The study involved 5137 patients with platelet counts >50 × 10⁹/L at enrollment. Severe TCP occurred in 597 subjects, and its incidence decreased over time. The incidence decreased in patients with opportunistic diseases and malignancies but increased in patients with chronic liver disease; TCP unrelated to any cause other than HIV infection remained stable. Multivariate analysis showed that injected drug use, a diagnosis of AIDS, low CD4⁺ cell counts, increased serum alanine aminotransferase levels, and an earlier year of enrollment were predictors of an increased risk of severe TCP, whereas the use of highly active antiretroviral therapy (HAART) was associated with a reduced risk., Conclusions: A considerable reduction in the incidence of severe TCP after the introduction of HAART was found, probably because of its ability to limit bone marrow damage induced by uncontrolled HIV replication and opportunistic infections. On the contrary, HAART may have a reduced impact on TCP related to chronic liver disease.