Annotated Abstracts of Journal Articles
2014, 2nd Quarter
Annotations by Oliver Freudenreich, MD, FAPM and Mary Ann Cohen, MD, FAPM
Also of interest:
Sexual transmission of HIV between women who have sex with women (WSW) is rare but it can occur. This case report to the CDC convincingly describes this mode of transmission in a woman who acquired HIV from her female partner during unprotected sex. Given the lack of other HIV risk factors and a phylogenetically virtually identical virus in this case, other explanations were not likely.
In an effort to reduce the number of new HIV infections (still about 50,000 per year), the CDC together with other federal agencies has updated their preexposure prophylaxis (PrEP) guidelines. Truvada (tenofovir/emtricitabine) is already approved for this indication but considered underutilized. According to the CDC, PrEP should be considered for patients at substantial risk for HIV infection (e.g., anyone in an ongoing relationship with an infected partner). Regular HIV testing (at baseline before PrEP and then every 3 months) is a critical part of this intervention to avoid virus resistance.
Ferrara M, Umlauf A, Sanders C, et al
Psychiatry Res 2014 Aug 15; 218(1-2):201-8
ANNOTATION (Freudenreich & Cohen)
The Finding: In a cohort of 2229 HIV-infected patients, 12% received second-generation antipsychotics (SGAs). Consistent with the side effect profile of SGAs, patients in this group (compared to patients not receiving SGAs) had higher mean triglyceride levels and a higher risk for DM. The majority of patients received quetiapine (almost 60%) at a mean dose of 241 mg/day.
Strength and Weaknesses: To my knowledge this is the first large data set that examines this clinically relevant question. Patients with schizophrenia were excluded (both a strength and a weakness) which suggest that many patients received antipsychotics for “softer” indications. The study was retrospective and cross-sectional.
Relevance: Psychiatrists and primary care doctors/ID doctors need to pay attention to the overlapping side effect profiles of second-generation antipsychotics and HAART with regards to dyslipidemia and the metabolic syndrome. Is the antipsychotic clearly indicated or needed? If yes, is metabolic monitoring done regularly? Two points made by the American Psychiatric Association when they contributed to the American Board of Internal Medicine’s “Choosing Wisely” campaign directly apply: 1) Don’t prescribe antipsychotic medications to patients for any indication without appropriate initial evaluation and appropriate ongoing monitoring; and 2) Don’t routinely prescribe antipsychotic medications as a first-line intervention for insomnia in adults. (For all 5 points see http://www.choosingwisely.org/doctor-patient-lists/american-psychiatric-association/.)
Objectives: To study the effect of concurrent use of second-generation antipsychotics (SGAs) on metabolic syndrome (MetS) components conferring increased cardiovascular risk in a sample of human immunodeficiency virus (HIV)-infected adults taking antiretroviral therapy (ART).
Methods: A retrospective study of participants consecutively recruited at the UCSD HIV Neurobehavioral Research Program examined effects of combined ART and SGAs on body mass index (BMI), nonfasting serum lipids, diabetes mellitus (DM) incidence, and mean arterial pressure (MAP). Metabolic outcome variables and covariates were compared using t-tests, Chi-squared or Fisher’s exact tests. Linear and logistic multivariable models explored metabolic outcomes for participants taking (SGA+) or not taking (SGA-) concomitant SGAs, after controlling for demographic and HIV disease- and ART-related covariates.
Results: Of 2229 HIV-infected participants, 12% (N=258) were treated with SGAs. In multivariable models adjusted for relevant covariates, the SGA+ group had significantly higher mean triglycerides, significantly higher odds of DM, significantly higher MAPs and marginally higher BMI. The use of SGAs in HIV-infected adults taking ART was independently associated with worse indicators of MetS and cardiovascular risk.
Conclusions: Aggressive monitoring for the metabolic complications from concurrent SGA and ART is indicated in all patients receiving these medication combinations.
ANNOTATION (Freudenreich & Cohen)
The Finding: In this longitudinal cohort study (the CHARTER cohort), a diagnosis of “asymptomatic neurocognitive impairment” (ANI) at the beginning of the study predicted, over a median follow-up of 45.2 months, progression to problems in everyday functioning. Combining self-report and performance-based measured, the presence of ANI conferred a relative risk of 3.0 (CI 2.1 to 4.4) when compared to patients without impairment at baseline.
Strength and Weaknesses: This is an important longitudinal study (as opposed to a cross-sectional study) with a sufficiently large sample of 121 patients diagnosed as ANI and 226 diagnosed as cognitively intact. The CHARTER cohort’s longitudinal design might be biased towards those people who can commit to participating in a longitudinal study (i.e., removing people at the extremes of function: those who work and those who are impaired).
Relevance: In HIV patients, preserving cognition remains elusive for some patients who, despite seemingly effective HIV treatment, develop functional impairments from HAND. It is a high priority to develop treatment strategies (either new drugs or optimizing current regimens for CNS protection) for patients that we label as having “asymptomatic neurocognitive impairment” (the majority of patients with HAND). There is value in diagnosing ANI: “Asymptomatic” might not sound alarming but as shown in the study, it is a risk factor for cognitive deterioration and we need to identify those patients even though they are currently “asymptomatic.” Research will eventually need to tell us what to do with them with regards to treatment, beyond merely monitoring their decline.
Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline).
Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD4+ T-lymphocyte count (CD4), virologic suppression, CART, and mood.
Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not.
Conclusions: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.