Carmen Bayón

Protease inhibitor monotherapy and the CNS: peace of mind?

Boosted protease inhibitor (bPI) monotherapy has demonstrated high efficacy for maintaining viral suppression in the blood. bPI monotherapy has the theoretical advantage of avoiding the long-term toxicity associated with the use of nucleoside reverse transcriptase inhibitors. Concern about the efficacy of bPI monotherapy in preventing HIV replication in the CNS is one reason that has precluded the widespread use of this therapeutic strategy. In several studies, a low CNS penetration-effectiveness (CPE) score has been associated with a higher risk of virological failure in the CNS and with neurocognitive impairment. Since the CPE score is substantially lower for bPI monotherapy than for triple-drug highly active antiretroviral therapy (HAART), it has been postulated that bPI monotherapy might have a higher risk for CNS virological failure and neurocognitive impairment. However, the available evidence, although limited, does no support this notion. Lopinavir and darunavir achieve CSF drug levels that are sufficient to fully suppress HIV replication. In clinical trials, when compared with triple-drug HAART, patients receiving bPI monotherapy with lopinavir and darunavir who maintain full virological suppression in plasma do not appear to be at a higher risk of discordant HIV replication in the CSF or of neuropsychiatric adverse events. It should be noted that several studies have suggested that nucleoside reverse transcriptase inhibitors might have neurotoxic effects and, consequently, bPI monotherapy might be able to avoid the CNS toxicity induced by nucleosides. It is clear that more studies including detailed neurocognitive testing are needed to completely establish the risk/benefit ratio of bPI monotherapy or triple-drug HAART for preserving neurocognitive function in HIV-infected patients.

Neurocognitive Impairment in Patients Treated with Protease Inhibitor Monotherapy or Triple Drug Antiretroviral Therapy

Background In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. Methods In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. Results Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15). Conclusions Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

A Prospective Cohort Study of Neurocognitive Function in Aviremic HIV-Infected Patients Treated With 1 or 3 Antiretrovirals

BACKGROUND The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. METHODS We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. RESULTS Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. CONCLUSIONS The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.

The revised Temperament and Character Inventory: normative data by sex and age from a Spanish normal randomized sample

Objectives. The psychometric properties regarding sex and age for the revised version of the Temperament and Character Inventory (TCI-R) and its derived short version, the Temperament and Character Inventory (TCI-140), were evaluated with a randomized sample from the community. Methods. A randomized sample of 367 normal adult subjects from a Spanish municipality, who were representative of the general population based on sex and age, participated in the current study. Descriptive statistics and internal consistency according to α coefficient were obtained for all of the dimensions and facets. T-tests and univariate analyses of variance, followed by Bonferroni tests, were conducted to compare the distributions of the TCI-R dimension scores by age and sex. Results. On both the TCI-R and TCI-140, women had higher scores for Harm Avoidance, Reward Dependence and Cooperativeness than men, whereas men had higher scores for Persistence. Age correlated negatively with Novelty Seeking, Reward Dependence and Cooperativeness and positively with Harm Avoidance and Self-transcendence. Young subjects between 18 and 35 years had higher scores than older subjects in NS and RD. Subjects between 51 and 77 years scored higher in both HA and ST. The alphas for the dimensions were between 0.74 and 0.87 for the TCI-R and between 0.63 and 0.83 for the TCI-140. Conclusion. Results, which were obtained with a randomized sample, suggest that there are specific distributions of personality traits by sex and age. Overall, both the TCI-R and the abbreviated TCI-140 were reliable in the ‘good-to-excellent’ range. A strength of the current study is the representativeness of the sample.

Facial Emotion Processing in Aviremic HIV-infected Adults

The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (≥2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy.

Facial emotional processing deficits in long-term HIV-suppressed patients.

Emotional processing is basic for social behaviour. We examine for the first time the facial emotion processing in long‐term HIV‐suppressed patients.