Journal Article Annotations
2019, 4th Quarter
Annotations by John Grimaldi, MD, Mary Ann Cohen, MD, FACLP, Kelly Cozza, MD, DFAPA, FACLP, and Luis Pereira, MD
Also of interest:
Substance use and psychiatric disorders are well-established risk factors for HIV acquisition and PLWH are more likely to have co-occurring psychiatric illness or problematic substance use compared to the general population. The ever-expanding list of available antiretroviral medications make it necessary for HIV healthcare providers to maintain up-to-date knowledge of potential drug-drug interactions between medications used to treat these co-existing conditions. This report offers a comprehensive summary of potential and known drug-drug interactions between psychotropic and antiretroviral medications. Using the PubMed/MEDLINE database, relevant articles were identified with priority given to human clinical pharmacokinetic and pharmacodynamic studies and secondarily toin vitrodata when clinical data were unavailable. Each major class of psychotropic medications and their subtypes are discussed: antidepressants, psychostimulants, antipsychotics, anxiolytics, mood stabilizers, as well as medications used to treat opioid and alcohol use disorders. Both psychotropic and antiretroviral medications undergo hepatic metabolism via the cytochrome P450 enzyme system. Individual medications and their corresponding substrates are identified and the strength of their ability to inhibit and/or induce specific P450 isoenzymes are described. This report’s detailed description of P450 involvement of individual medications may serve as a reference for predicting pharmacokinetic interactions of future antiretroviral medications. In addition, compounding adverse effects of interacting drugs are discussed. Notable examples include overlapping neuropsychiatric toxicities with psychostimulants and efavirenz and rilpivirine, increased risk for torsades de pointes with citalopram and escitalopram and saquinavir mediated through QT interval prolongation, and metabolic syndrome that is associated with both second generation antipsychotic medications as well as antiretroviral therapy. The consequences of nonadherence to antiretroviral therapy due to overlapping toxicities and the potential development of viral resistance from inadequate antiretroviral blood levels compel clinicians to consider drug-drug interactions in the management of psychiatric morbidity in an HIV clinical setting.
AIDS Behav. 2019 Oct;23(10):2859-2869. doi: 10.1007/s10461-019-02464-1.
This cross-sectional secondary analysis of baseline data from Project Hope, a randomized, controlled intervention trial targeting viral suppression in people living with HIV (PLWH), examined associations between patient mistrust of both their physicians as well as the healthcare system and their engagement in HIV care. Participants were HIV-infected individuals with substance use and poor virologic control. The greater the degree of physician mistrust, the less likely it was for participants to be engaged in care as measured by never having seen an HIV provider and time elapsed since last office visit. Homelessness and living in the Southern U.S. were also significantly associated with these measures. The significant positive association between physician mistrust and viral load may be mediated through longer time elapsed since seeing an HIV provider. Compared to non-Caucasians, Caucasians were more likely to report discrimination based on sexual orientation or drug use.
Strength and weaknesses:
Study participants comprised a large, diverse sample of PLWH with comorbid substance use and poor virologic control from 11 states across the U.S. and were drawn from the largest study to date of PLWH with substance use and poorly controlled infection. A large proportion of participants were male and homeless with a low educational level, members of racial/ethnic minorities, and living in the southern U.S. Separate measures used for mistrust of one’s physician, mistrust of the healthcare system and experiences of discrimination will enable development of interventions targeting each factor and their corresponding influence on health care utilization and ultimately viral suppression. The study’s cross-sectional design limits conclusions about the chosen variables’ causal effects on engagement in care. The measurement tools’ reliance on self-report introduces a bias effect, even though some measures significantly correlated with medical record review. Measures related to engagement in care such as time elapsed since last HIV primary care visit were retrospective rather than prospective. Measures related to mistrust of health care professionals and the health system did not allow for conclusions about mistrust based on other factors such as sexual orientation, gender, substance use or HIV status. Additionally, racial/ethnic concordance between patient and physician, which is known to influence the relationship, was not assessed. Given the specific characteristics of the study sample, findings are not generalizable to a broader population of PLWH.
Following a period of declining rates of new HIV infections in the U.S. across all risk groups, more recent numbers of new infections have stabilized. One explanation for this slowing reduction in transmission suggests that current strategies to prevent HIV and engage PLWH in care may not be reaching at risk subpopulations. This study aims to understand factors that may influence engagement of vulnerable populations across the full continuum of HIV care. The study findings also suggest potential targets for interventions that may mitigate risk factors that were identified. The success of the national strategy, Ending the HIV Epidemic in America by the end of the next decade will depend on finding innovative approaches to preventing and treating people at risk for and living with HIV affected by multiple syndemic conditions such as substance use, homelessness, and belonging to racial/ethnic and sexual minorities. One unanticipated finding was that those PLWH with more severe drug use problems were more likely to be engaged in care, suggesting that substance use treatment may provide an entry point into HIV care. It also strengthens the case for an approach that integrates HIV and substance use treatment. This study is consonant with findings from previous research linking a positive patient-physician relationship and favorable outcomes in many other medical and psychiatric conditions and confirms the deleterious impact of substance use’s “double stigma” in PLWH. However, there is a significant research gap examining the effect of patient mistrust of physicians in determining outcomes among PLWH with various syndemic conditions. These findings provide a basis for research that aims to identify active ingredients to a trusting therapeutic relationship and intervention trials that test the effect of improved physician, patient-centered communication skills on medical outcomes and virologic control.
Type of study:
This study is a cross-sectional secondary analysis of baseline data from Project Hope, a randomized, controlled intervention trial targeting viral suppression in people living with HIV (PLWH).
JAMA Psychiatry.2019 Dec 11. doi: 10.1001/jamapsychiatry.2019.3655. (Epub ahead of print)
This double-blind, randomized placebo-controlled trial tested the efficacy of mirtazapine in reducing use of methamphetamine and sexual risk behaviors in cisgender men and transgender women who have sex with men. Over half of the participants were HIV-infected and eligibility required a DSM-IV-TR diagnosis of methamphetamine dependence. Participants also received substance use counselling using cognitive-behavioral therapy and motivational interviewing. The primary outcome measure was methamphetamine-positive urine drug screens which were obtained weekly, while secondary outcomes comprised sexual risk behaviors. There was a significant decline in methamphetamine-positive urine drug screens at week 12 and week 24 (study end-point), in the mirtazapine arm vs placebo. This effect was maintained at week 36, 12 weeks after the end of the study. The mirtazapine arm did not show a significant decrease in any sexual risk behaviors until week 24: reduction in number of male sexual partners, partners who were serodiscordant with whom participants had condomless anal sex, and partners who were discordant with whom participants had condomless receptive anal sex. These differences were not maintained at week 36. Depression and insomnia scores were improved only at week 24 and failed to show significance at weeks 12 and 36. Medication adherence did not differ between study arms at both weeks 12 and 24 and there were no serious adverse effects associated with mirtazapine.
Strengths and limitations:
This study is the first double-blind, randomized placebo-controlled trial to show that mirtazapine is an effective pharmacotherapeutic agent for methamphetamine- dependent men and transgender women who have sex with men. The positive findings replicate and expand on a smaller study by the same research group that found a significant decrease in methamphetamine-positive urine drug screens and sexual risk behaviors after 12 weeks of treatment with mirtazapine. The study has several limitations. Findings may not apply to a broader population of individuals with methamphetamine dependence such as men who have sex with women only or cisgender women who have sex with men. Findings may also not generalize to individuals with mild-moderate methamphetamine use. Since individuals with major depression were excluded from participation, findings may not apply to the substantial subgroup of methamphetamine users who are depressed. The clinical significance of the positive effects of mirtazapine remain unknown and require further study.
Prevalence rates of methamphetamine use among men who have sex with men have been as high as 11-13% in some studies. Methamphetamine use is associated with HIV sexual and injection drug risk behaviors, and psychiatric and medical comorbidity, such as persistent psychotic states and impaired immune cell function. Among men who have sex with men living with HIV, comorbid methamphetamine use is associated with neurotoxicity, poor antiretroviral adherence, virologic nonsuppression and accelerated disease progression. Sustained virologic suppression is a cornerstone of the Ending the HIV Epidemic in America strategic plan which further highlight’s this study’s relevance. There are currently no approved pharmacotherapies for the treatment of methamphetamine use disorders and only limited research examining effectiveness of psychosocial interventions. This study also addresses safety concerns about prescribing psychotropic medications such as mirtazapine in the setting of ongoing methamphetamine use. Additionally, this study suggests that mirtazapine may be applicable to patients who prefer a harm reduction treatment approach to methamphetamine use since the primary outcome was decreased use rather than abstinence.
Type of study:
This was a double-blind, randomized placebo-controlled efficacy and safety trial of mirtazapine for methamphetamine dependence in cisgender men and transgender women who have sex with men.