Fundacion Arriarán

The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.

It has been estimated that between 15% and 18% of patients who start antiretroviral therapy (ART) do not achieve a successful immune recovery despite complete virological suppression. In the literature this phenomenom is known as poor immune recovery or immunovirological discordance (IVD). Zinc has an immunomodulatory role associated with T lymphocytes and its supplementation could enhance immune recovery. OBJECTIVE:to determine if zinc supplementation on IVD patients prevents immune failure after 12 months of supplementation. Secondary objectives were to determine serum zinc levels in HIV patients with and without IVD and the frequency of hypozincemia in discordant patients.METHOD: we reviewed the historical record of patients under care at Arriarán Foundation. Following inclusion criteria were defined: 1) age>18 years, 2) standard ART (three effective drugs) for at least 18 months, 3) virologically suppressed for 12 months, 3) persistence of CD4 count<200 cells/mm3and/or increase<80 cells/mm3after one year of viral undetectability. A control group was assigned paired 1:1 by sex, age (+2 years) that did achieved an increase of CD4> 350 cells/ mm3. In both groups plasma zinc levels were determined. In a later phase, patients with IVD were randomized to receive zinc (15 mg daily) versus placebo. Patients were followed for 12 months with CD4 count, viral load and zinc levels determinations every 4-6 months. RESULTS: a total of 80 patients, 40 patients with IVD criteria and 40 controls were included. 92.5% were men, and age average was47.5years. The median baseline CD4 was189cells/mm3(71-258) in the cases vs.552.5cells/ mm3(317-400) in the controlgroup with a total increase at the end of the study of 34 cell/mm3and 30 cell/mm3respectively.There was no difference in baseline plasma zinc levels between both groups (81.7 + 18.1in cases versus86.2 + 11.0in controls).In the 40 patients with IVD, the median absolute increase in CD4 after annual zinc supplementation was31.5cells/mm3in the treated group versus50cells/mm3in the placebo group, this difference being statistically not significant(p = 0.382).CONCLUSIONS: Patients with IVD have plasma zinc levels similar to those who achieve adequate immune recovery.Zinc supplementation in IVD patients showed a statistically non-significant increase in CD4 levelsbetween cases and controls. The results warrant a comparative study with a larger number of patients.

Accelerating antiretroviral therapy (ART) administration, improving retention, and achieving viral suppression in low- and middle-income countries must be prioritized. We evaluated trends and disparities in these milestones in a large Latin American cohort. Adults starting ART (ARTstart) from 2003 to 2014 at Caribbean, Central, and South America network for HIV epidemiology sites were assessed for care cascade outcomes: CD4 cell count >200 cells/mm3 at ARTstart; retention (≥1 visit at one year after ARTstart); viral suppression (≥1 HIV-1 RNA <200 copies/ml at one year after ARTstart). Modified Poisson regression provided adjusted prevalence ratios by age, gender, and HIV transmission risk, accounting for site and year of ARTstart. Proportions achieving ARTstart and suppression improved over time (p < 0.05). Older age was associated with better retention and viral suppression, but not ARTstart at CD4 cell count >200 cells/mm3. Females and men who have sex with men (MSM) were more likely to have CD4 cell count >200 cells/mm3 at ARTstart. Injection drug users (IDUs) were less likely to be retained while MSM were more likely to achieve viral suppression (all p < 0.05). Despite improvements in these outcomes over the course of a decade in this cohort, significant disparities existed, disadvantaging younger patients, men, and IDUs. These gaps indicate continued progress in providing early diagnosis and ARTstart remain critical.

To explore the effect of demographics and single-nucleotide polymorphisms in cytochrome P450 (CYP) 2B6, 2A6, UDP-glucuronosyltransferase (UGT) 2B7, and the constitutive androstane receptor (CAR) genes on efavirenz pharmacokinetics in a Chilean cohort affected with human immunodeficiency virus. Timed plasma samples obtained throughout the dosing interval were analyzed for efavirenz concentrations with liquid chromatography/tandem mass spectrometry. DNA from whole-blood samples was used for genetic analysis. Data were analyzed using a Mann-Whitney statistical test; furthermore, a Pearson or Spearman correlation was used. A multivariate analysis was then conducted using multiple linear regression by best subset analysis. Overall 219 patients were included, 208 patients had measurable efavirenz levels and available genetic samples. The overall median (interquartile range) of efavirenz concentration was 2.6 (2.1-3.7) mcg/mL. In multivariate regression analysis, CYP2B6 516G>T (P < 0.0001) and CAR rs2307424 C>T (P = 0.002) were significantly related to efavirenz plasma concentrations. This novel association between CAR rs2307424 and efavirenz plasma concentrations now requires validation in other cohorts.