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Annotated Abstracts of Journal Articles
2015, 1st Quarter

HIV Psychiatry

Annotations by Oliver Freudenreich, MD, FAPM and Mary Ann Cohen, MD, FAPM
March 2015

  1. Cognitive function in women with HIV: findings from the Women's Interagency HIV Study
  2. Human immunodeficiency virus transmission at each step of the care continuum in the United States

Also of interest:

  • Brezing C, Ferrara M, Freudenreich O: The Syndemic illness of HIV and trauma: implications for a trauma-informed model of care
    Psychosomatics 2015; 56(2):107-118

    In this extensive literature review, highly variable rates of trauma were found in patients infected with HIV, ranging from 10 to 90%. Regardless of the practice setting, trauma will thus play a role in at least a minority of patients or in the vast majority of patients a clinician encounters. It might be prudent to incorporate elements of trauma-informed care when treating patients with HIV. Clinicians unfamiliar with trauma-informed care can get more information from the National Center for Trauma-Informed Care on the SAMHSA website. (Disclosure: Annotator Oliver Freudenreich is one of the co-authors of the literature review.)

  • Chhatwal J, Kanwal F, Roberts MS, Dunn MA: Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States
    Ann Intern Med 2015 Mar 17; 162(6):397-406

    This is a highly technical paper about the cost-effectiveness of one of the new oral hepatitis C treatments compared to the old standard of care with interferon. Given substantial numbers of patients with HIV-HCV co-infection, the article should also be of interest to any HIV clinician or administrator who wants to understand the financial impact of providing hepatitis C treatment with the new oral regimens, particularly with regards to different thresholds for cost-effectiveness. Using a “willingness-to-pay” threshold of $100,000 (which is higher than the perhaps unrealistic, customary threshold of $50,000), treatment with sofosburi-ledipasvir (which costs $1125 per day) was cost-effective for most patients. The article also confirms what might be self-evident and what we have already seen in selected markets: that a new and highly effective yet very expensive treatment like oral combination treatment for hepatitis C would have a huge budget impact now if everybody were treated. The authors estimate that providing the new treatment would cost an additional $65 billion over the next 5 years while offsetting only $16 billion of the overall cost of HCV care. The logical conclusion is this: if prices do not come down, we can only afford these new treatments if we either get more money to pay for the treatments or prioritize patients, the latter also known as rationing.

PUBLICATION #1 — HIV Psychiatry
Cognitive function in women with HIV: findings from the Women's Interagency HIV Study

Maki PM, Rubin LH, Valcour V, Martin E, Crystal H, Young M, et al
Neurology 2015 Jan 20; 84(3):231-40

ANNOTATION (Freudenreich & Cohen)

The Findings: HIV status per se contributed very little (effect size using Cohen’s d less than 0.20) to cognition in women who participated in the Women’s Interagency HIV Study (WIHS). The effects of HIV infection were most evident in women with low reading levels and if they had HIV-associated comorbidities.

Strength and Weaknesses: This is the largest study of comprehensively assessed cognition in American, urban dwelling women in the United States, comparing women with and without HIV. Most were minorities, and almost half of the sample was living in poverty. The study results reported here used a cross-sectional design and did not cover the full spectrum of severity with regards to cognition (i.e., women with dementia were not included) and immune function (i.e., the majority of woman had a CD4 count above 200 which might not lead to cognitive problems until later in the course of illness). As this is a cohort study, survivor bias (i.e., an underrepresentation of women with more serious problems) might be at play.

Relevance: Low educational achievement and quality of education (as judged by reading levels) magnify cognitive difficulties related to HIV infection, but the differences in cognition between women with or without HIV are not striking, at least not for HIV-infected women who have good immune function. Put differently, this observation is consistent with the idea that high educational achievements provide a buffer (cognitive reserve) that can compensate for any HIV-associated cognitive problems, at least to some extent during the early phase of infection when HIV-related damage to the brain is not at the level of clinical disorder like HAND. The finding is reminiscent of the protective effects of education with regards to Alzheimer’s disease. Most importantly, the study is a reminder that cognition and neurocognitive test results cannot be understood in a vacuum but only by taking into account education and social factors. The social determinants of (brain) health matter for cognition in women infected with HIV.


Objective: In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2).

Methods: From 2009 to 2011, 1,521 (1,019 HIV-infected) participants from the Women's Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional.

Results: The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction.

Conclusions: The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in well-matched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition.

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PUBLICATION #2 — HIV Psychiatry
Human immunodeficiency virus transmission at each step of the care continuum in the United States

Skarbinski J, Rosenberg E, Paz-Bailey G, Hall HI, Rose CE, Viall AH, et al
JAMA Intern Med 2015; 175(4):588-96

ANNOTATION (Freudenreich & Cohen)

The Findings: Using the framework of the HIV treatment cascade, the authors used national surveillance data to estimate the risk of HIV transmission for each of the steps of the care continuum. Of the 45,000 HIV transmissions in 2009, 91.5% were attributable to patients with HIV who were undiagnosed (18% of the population) or not retained in medical care (45% of the population).

Strength and Weaknesses: This was a very large data set that nevertheless could not account for all factors associated with transmission. It also provides a static, population-based view that cannot be used for individual-level assessment of transmission risk. The authors also had to use a definition of retention (one visit to an HIV care provider in the first 4 months of the year) that might overestimate the number of patients not retained in care.

Relevance: Early diagnosis (i.e., screening) is a necessary but not sufficient component of HIV care if we want to reduce the number of new HIV infections. Most transmissions (61.3%) were attributable to patients identified as HIV positive but not retained in care. The good news in this report is the following: those patients who are diagnosed, retained in care, on cART, and who have achieved viral suppression are much less likely to transmit HIV compared to those who are undiagnosed. Treatment as prevention does work for those who are in treatment who receive and adhere to effective treatment.


Importance: Human immunodeficiency virus (HIV) transmission risk is primarily dependent on behavior (sexual and injection drug use) and HIV viral load. National goals emphasize maximizing coverage along the HIV care continuum, but the effect on HIV prevention is unknown.

Objectives: To estimate the rate and number of HIV transmissions attributable to persons at each of the following 5 HIV care continuum steps: HIV infected but undiagnosed, HIV diagnosed but not retained in medical care, retained in care but not prescribed antiretroviral therapy, prescribed antiretroviral therapy but not virally suppressed, and virally suppressed.

Design, Setting, and Participants: A multistep, static, deterministic model that combined population denominator data from the National HIV Surveillance System with detailed clinical and behavioral data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project to estimate the rate and number of transmissions along the care continuum. This analysis was conducted January 2013 to June 2014. The findings reflect the HIV-infected population in the United States in 2009.

Main Outcomes and Measures: Estimated rate and number of HIV transmissions.

Results: Of the estimated 1 148 200 persons living with HIV in 2009, there were 207 600 (18.1%) who were undiagnosed, 519 414 (45.2%) were aware of their infection but not retained in care, 47 453 (4.1%) were retained in care but not prescribed ART, 82 809 (7.2%) were prescribed ART but not virally suppressed, and 290 924 (25.3%) were virally suppressed. Persons who are HIV infected but undiagnosed (18.1% of the total HIV-infected population) and persons who are HIV diagnosed but not retained in medical care (45.2% of the population) were responsible for 91.5% (30.2% and 61.3%, respectively) of the estimated 45 000 HIV transmissions in 2009. Compared with persons who are HIV infected but undiagnosed (6.6 transmissions per 100 person-years), persons who were HIV diagnosed and not retained in medical care were 19.0% (5.3 transmissions per 100 person-years) less likely to transmit HIV, and persons who were virally suppressed were 94.0% (0.4 transmissions per 100 person-years) less likely to transmit HIV. Men, those who acquired HIV via male-to-male sexual contact, and persons 35 to 44 years old were responsible for the most HIV transmissions by sex, HIV acquisition risk category, and age group, respectively.

Conclusions and Relevance: Sequential steps along the HIV care continuum were associated with reduced HIV transmission rates. Improvements in HIV diagnosis and retention in care, as well as reductions in sexual and drug use risk behavior, primarily for persons undiagnosed and not receiving antiretroviral therapy, would have a substantial effect on HIV transmission in the United States.


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