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Evolution of changes in cognitive function after the initiation of antiretroviral therapy.

ABSTRACT: BACKGROUND:Cognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART. METHODS:Cognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive scores were transformed using standardised z-scores according to the pooled baseline standard deviation. Global, speed, and accuracy composite z-scores were calculated with changes calculated using a paired t test. RESULTS:In 14 subjects, change in global cognitive z-scores from baseline was by 0.08 at week 24 (p = 0.59) and 0.15 at week 48 (p = 0.43). Change in composite speed and accuracy z-scores from baseline at weeks 24/48 were 0.07/0.05 (p = 0.45/0.82) and 0.13/0.23 (p = 0.47/0.45), respectively. In two of the cognitive domains assessing speed (learning and monitoring time), a continued improvement from baseline to weeks 24 and 48 was observed (changes of 0.06-0.08 and 0.10-0.19, respectively), whereas in two domains (detection and identification) an initial improvement at week 24 (changes of -0.10 and 0.04 from baseline, respectively) was followed by a deterioration in score at week 48 (changes of -0.12 and -0.08 from baseline, respectively). None of these changes were statistically significant. CONCLUSIONS:A trend for improvement in cognitive function was observed in naïve HIV-positive patients starting cART. The dynamics of this improvement differed both between cognitive domains and the time-points assessed.

SUBMITTER: Mora-Peris B

PROVIDER: S-EPMC4831200 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Evolution of changes in cognitive function after the initiation of antiretroviral therapy.

Mora-Peris Borja B Stevens Elizabeth E Ferretti Francesca F Underwood Jonathan J Taylor Stephen S Winston Alan A

AIDS research and therapy 20160414

<h4>Background</h4>Cognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART.<h4>Methods</h4>Cognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive score ...[more]

PMID: 27081393

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Project description:ImportanceDespite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear.ObjectiveTo determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART.Design, setting, and participantsIn this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses.Main outcomes and measuresBrain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection.ResultsThe 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P = .01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P < .001), Digit Symbol Substitution Task (-12.5 marks; 95% CI, -18.9 to -6.0; P < .001), Letter-Number Sequencing (-2.5 marks; 95% CI, -3.7 to -1.3; P < .001), Letter Fluency (-6.6 words; 95% CI, -11.5 to -1.6; P = .01), and Hopkins Verbal Learning Test-Revised immediate recall (-2.4 words; 95% CI, -4.4 to -0.4; P = .05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups.Conclusions and relevanceThese findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.

Project description:IntroductionWeight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV-positive individuals.MethodsThis was a prospective cohort study of 13,198 subjects included in the Spanish HIV Research Network (CoRIS) between January 2004 and November 2018. We included subjects who started triple ART and achieved HIV RNA suppression within 48 weeks. We fitted linear mixed models adjusted for potential confounders to compare longitudinal changes in weight. We used Cox proportional-hazard models to compare treatment groups' times to transition to a higher body mass index (BMI) category.ResultsWe analysed data from a total of 1631 individuals resulting in 14,965 persons/years and 14,085 observations. Individuals retained in the final multivariable model were representative of the overall cohort. NNRTI-based first-line ART was associated with a lower average weight gain compared to PI- (+0.7 kg per year, 95% CI 0.5 to 1.0, p < 0.001) and INSTI-based (+0.9 kg per year, 95% CI 0.7 to 1.1, p < 0.001) regimens. Individuals starting ART with TAF+FTC had greater weight gain than those receiving TDF+FTC (+0.8 kg per year, 95% CI 0.3 to 1.4, p = 0.004). Women and black persons presented a greater weight gain than men and non-black individuals. Differences in weight trajectories were driven mainly by changes during the first year of ART. The NNRTI group was less likely to transition from normal weight to overweight than the PI (aHR 1.48, 95% CI 1.18 to 1.85) and INSTI groups (aHR 1.30, 95% CI 1.03 to 1.64). PIs but not INSTIs were associated with a higher rate of overweight-to-obesity shift (aHR 2.17, 95% CI 1.27 to 3.72). No differences were found among INSTIs in the transition to a higher BMI category.ConclusionsINSTI- and PI-based first-line ARTs are associated with greater weight gain compared to NNRTI-based ART. Within the NRTIs, TAF+FTC was most strongly associated with weight gain. This heterogeneous effect of ART on body weight could affect the long-term risk of some non-communicable diseases.

Project description:BACKGROUND:Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS:We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS:A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS:The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

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Evolution of changes in cognitive function after the initiation of antiretroviral therapy.

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Evolution of changes in cognitive function after the initiation of antiretroviral therapy.

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