Journal Article Annotations
2022, 4th Quarter
Annotations by John A R Grimaldi, MD, Mary Ann Cohen MD, FACLP, Kelly Cozza MD, DLFAPA, FACLP, Luis Pereira, MD
Data from the Women’s Interagency HIV Study (WIHS) were used to examine associations between Efavirenz and Integrase Strand Transfer Inhibitors (INSTIs) and adverse neuropsychiatric effects. Participants were divided into 5 previously defined subgroups that differed by sociodemographic factors and longitudinal behavioral and clinical characteristics. The Perceived Stress Scale-10 and PTSD Checklist-Civilian were used to measure anxiety symptoms and symptoms of re-experiencing, avoidance, and hyperarousal. There was a significant association between dolutegravir and elvitegravir and stress/anxiety and avoidance symptoms in the subgroup of participants with the highest percentage of women with CD4 nadir < 250. There was also an association between elvitegravir and re-experiencing symptoms in this subgroup. In the subgroup of women with the greatest percentage of well-controlled HIV, elvitegravir was significantly associated with re-experiencing and hyperarousal symptoms. Raltegravir was associated with less hyperarousal among the subgroup of women younger than 45 years old and who were more likely to have comorbid hepatitis C. No significant associations were found between any of the INSTIs and stress symptoms in either the subgroup comprising 35-55 year-old women or the subgroup with the highest percentage of participants with poorer HIV clinical characteristics and substance use. None of nonnucleoside reverse transcriptase inhibitors (NNRTIs) were associated with symptomatology. Efavirenz was not associated with either greater or lower adverse neuropsychiatric effects in any of the subgroups. This finding was surprising in light of Efavirenz being the antiretroviral drug most commonly associated with adverse effects: vivid dreams, insomnia, dizziness, fatigue and suicidality. Although not of primary interest in this study, nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir and abacavir, were associated with less neuropsychiatric effects in certain subgroups. The protease inhibitor atazanavir showed associations in both directions that varied by subgroup.
Strengths and limitations:
This large-scale study used data from the largest female cohort of people with HIV to date. It is the first study to examine the link between efavirenz and INSTIs and anxiety and PTSD symptoms in subgroups of women defined by sociodemographic factors, longitudinal behavioral, and clinical characteristics. Previous studies have demonstrated that depressive and cognitive symptoms secondary to antiretroviral medications, such as efavirenz, are variable depending on race/ethnicity. Findings from this study may similarly inform a more personalized medicine approach to INSTI-based regimens. This study employed advances in computational modeling and bioinformatics that facilitated identification of links among specific antiretroviral medications, neuropsychiatric symptoms, patient and HIV-related factors. Because not all participants were evaluated on all antiretroviral medications, interpretation of study results was limited. Additionally, findings applied only to women and were not generalizable to men.
Adverse effects of antiretroviral medications are a well-documented reason for treatment discontinuation. The majority of studies addressing this problem has involved only men and are not generalizable to women. Findings from this study may facilitate better tolerated medication choices. The study also demonstrated a method of statistical analysis that may promote personalized medicine with other populations.
This paper is structured review of HIV literature from 2015-2020 across many key populations (surprisingly 19 focused on teens and adolescents), associated health conditions that included SMI, and an emphasis on studies that evaluated HIV prevention and risk reduction while also including mental health parameters. Fifty papers met inclusion criteria for full review, of which 26 were randomized controlled trials (RCTs) and/or experimental designs (had pre-post-intervention evaluations). Many of the reviewed studies supported the need for more finely integrated approaches between primary and mental health care in order to improve HIV prevention and outcomes. Depression, anxiety, and serious mental illness (SMI) continues to greatly impact HIV prevention and treatment.
Strengths and weaknesses:
The presentation of these findings is burdened by a reliance on tables. The reader will benefit from focusing on Table 2, “Mental Health Outcomes” and “HIV Outcomes” in the “MH baseline prevalence and HIV/MH key findings” column. This paper includes many different types of studies and is commendable for its global approach.
An important collection of papers remind us about the bio-psycho-socio-cultural elements related to the care of persons with HIV: “60% of new HIV infections occur among key populations and their sexual partners, including gay men and other men who have sex with men (MSM), female sex workers (FSW), transgender women (TGW) (primarily), people who inject drugs (PWID), and prisoners and other incarcerated people” (Collins et al, 2021, p4). This is a very nice collection to have at one’s fingertips about the available literature related to mental health and interventions in HIV care. The authors have supported what we all know with a nice review of the literature: those with SMI/severe depression demonstrate fewer HIV prevention behaviors, and “In all but one study, depression impaired PrEP adherence. In the majority of HIV testing and counselling studies, having fewer symptoms of a mental disorder increased HIV testing. Depressive, anxiety and trauma symptoms usually reduced the likelihood of condom use or condom self-efficacy” (Collins et al, p31).
Psychotropics and antiretrovirals are potent risk factors for medication-induced hyperglycemia and glucose dyscontrol. This helpful review concisely summarizes how second-generation antipsychotics (SGAs), antiretrovirals (ARVs), and immune checkpoint inhibitors (ICIs) (chemotherapeutic agents) impact glucose control and elucidates their relevant mechanisms of action. Several key points follow: SGAs are noted exert their effects on glucose control by affecting “cellular insulin signalling, endogenous glucose production, glucose uptake and insulin secretion, thus implicating different key organs (liver, skeletal muscle and endocrine pancreas). The primary defect in insulin signalling appears to be a marked impairment of post-receptor IRS-1 phosphorylation. Downregulation of intracellular downstream biochemical pathways subsequently occurs…” Older ARVs, such as first-generation nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) and Protease Inhibitors (PIs) all greatly affect glucose metabolism, causing lipoatrophy and trunk fat hypertrophy, and efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) alters adipocyte development and function. The authors also remind the reader that INSTIs such as dolutegravir and raltegravir may also cause increased adiposity.
Strength and weaknesses:
The paper summarizes the impact of these medications on glucose control, and the authors discuss how behavioral change and medication can mitigate the effects of other medications. The authors pose a brief and simplified approach to a complicated topic that is easily accessible.
A very nice review of diabetogenic medications that includes HIV treatment medications and antipsychotics. This is a nice overview paper to share with primary care colleagues and trainees. This paper also has a simple (and downloadable) diagram depicting the mechanisms of drug-induced hyperglycemia for use in teaching.