Altered neuropsychological performance and reduced brain volumetrics in people living with HIV on integrase strand transfer inhibitors

AbstractIntegrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

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An observational study of the prevalence of metabolic syndrome in treatment-experienced people living with HIV in Singapore

PLoS ONE ◽

10.1371/journal.pone.0252320 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252320

Author(s):

Li Wei Ang ◽

Oon Tek Ng ◽

Irving Charles Boudville ◽

Yee Sin Leo ◽

Chen Seong Wong

Keyword(s):

Metabolic Syndrome ◽

Protease Inhibitors ◽

Drug Effects ◽

People Living With Hiv ◽

Strand Transfer ◽

Metabolic Complications ◽

Obesity And Diabetes ◽

Living With Hiv

Background While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore. Methods We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015–2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes. Results A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%–25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%). Conclusion MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV.

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Increase in visceral adipose tissue in a woman living with HIV after introduction of integrase strand transfer inhibitor

International Journal of STD & AIDS ◽

10.1177/0956462420955075 ◽

2020 ◽

Vol 31 (14) ◽

pp. 1407-1410

Author(s):

Daniela Piacentini ◽

Massimiliano Lanzafame ◽

Sebastiano Rizzardo ◽

Sheila Chiesi ◽

Emanuela Lattuada ◽

...

Keyword(s):

Adipose Tissue ◽

Antiretroviral Drugs ◽

Strand Transfer ◽

Metabolic Abnormalities ◽

Tissue Density ◽

Integrase Strand Transfer Inhibitors ◽

Transfer Inhibitor ◽

Living With Hiv ◽

Visceral Adipose ◽

Integrase Strand Transfer Inhibitor

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral drugs with high virologic efficacy and excellent tolerability. Recent evidence showed a possible link of dolutegravir-based regimens with weight gain, and a relationship between raltegravir use and changes in adipose tissue density and metabolic abnormalities, with an increased cardiovascular risk, has been suggested. We describe a case where dolutegravir monotherapy led to a decrease in adipose tissue density.

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Clinical Safety Considerations of Integrase Strand Transfer Inhibitors in the Older Population Living with HIV

Drugs & Aging ◽

10.1007/s40266-021-00894-y ◽

2021 ◽

Author(s):

Etty Vider ◽

Elizabeth Marie Gavioli

Keyword(s):

Strand Transfer ◽

Older Population ◽

Clinical Safety ◽

Integrase Strand Transfer Inhibitors ◽

Safety Considerations ◽

Living With Hiv

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Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study

BMJ Open ◽

10.1136/bmjopen-2019-031487 ◽

2020 ◽

Vol 10 (3) ◽

pp. e031487

Author(s):

Barbara N Harding ◽

Bridget M Whitney ◽

Robin M Nance ◽

Heidi M Crane ◽

Greer Burkholder ◽

...

Keyword(s):

Cohort Study ◽

Proportional Hazards ◽

Transcriptase Inhibitor ◽

Severe Anaemia ◽

Cox Proportional Hazards ◽

People Living With Hiv ◽

Strand Transfer ◽

Clinical Cohort ◽

Increased Risk ◽

Living With Hiv

ObjectiveAnaemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era.DesignRetrospective cohort study.SettingUSA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018.Participants16 505 PLWH were included in this study.Main outcome measuresAnaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change.ResultsDuring a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use.ConclusionThese findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

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Overweight, Obesity, and Neuropsychological Performance: Results From the Women’s Interagency HIV Study

Innovation in Aging ◽

10.1093/geroni/igab046.667 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 176-177

Author(s):

Elizabeth Vasquez ◽

Mark Kuniholm ◽

Leah Rubin ◽

Anjali Sharma ◽

Kathleen Weber ◽

...

Keyword(s):

Executive Function ◽

Motor Function ◽

Processing Speed ◽

Linear Models ◽

Normal Weight ◽

Aging Brain ◽

People Living With Hiv ◽

Neuropsychological Performance ◽

Hiv Women ◽

Living With Hiv

Abstract Conflicting associations of body mass index (BMI) and waist circumference (WC) with neuropsychological performance (NP) are observed in the general population and among people living with HIV. We examined BMI and WC in middle-aged women living with HIV (WLWH) and without HIV (HIV-) in relation to 10-year trajectories of NP in the Women’s Interagency HIV Study (WIHS). NP assessments occurred biennially from 2009-2019. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear models stratified by HIV serostatus examined whether baseline (2009) BMI and WC were associated with NP domains - 1) cross-sectionally and 2) longitudinally over 10 years. The sample included 432 WLWH and 367 HIV- women, >40 years old. Most women (73%) were overweight (BMI=25-29.9kg/m2) or obese (BMI=>30kg/m2). Among WLWH, 28% were overweight, 45% obese; among HIV- women, 26% were overweight; 56% obese. Cross-sectionally at baseline, WLWH who were overweight versus normal weight (BMI=18.5-24.9kg/m2), performed worse on executive function, processing speed, and motor function (all p<0.05). HIV- women who were overweight versus normal weight performed worse on memory, learning, executive function, processing speed and motor function (all p<0.05). Baseline BMI and WC were not associated with worsening NP domains in this younger, primarily overweight and obese sample of WLWH or HIV- women (all p>0.05).Future follow-up of these women will enhance understanding of the age when total and/or central obesity may influence NP trajectories and health of the aging brain.

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Continuum of Care UNAIDS Fast-Track Targets Evaluation of Patients Living with Human Immunodeficiency Virus Infection

Healthcare ◽

10.3390/healthcare9101249 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1249

Author(s):

Cristian Jianu ◽

Corina Itu-Mureşan ◽

Adriana Violeta Topan ◽

Irina Filipescu ◽

Mihaela Elena Jianu ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Fast Track ◽

Hiv Transmission ◽

Strand Transfer ◽

Nations Programme ◽

United Nations Programme ◽

Immunodeficiency Virus ◽

Integrase Strand Transfer Inhibitors ◽

Living With Hiv

The current study evaluated the progress of continuum healthcare for patients living with human immunodeficiency virus (HIV) infection from Cluj County in two moments, 2016 and 2020, and compared the results to the Fast-Track targets (FTTs) proposed by the Joint United Nations Programme (UNAIDS) on HIV/AIDS. By the end of 2020, 368 out of 385 confirmed HIV-positive patients from Cluj County were under surveillance in our center, representing almost 95% of the patients living with HIV and knowing their diagnosis, compared to 87.9% in 2016. Nearly 97% of those in active follow-up from Cluj County were under antiretroviral therapy (ART) in 2020, compared to 89% in 2016. The number of virally suppressed patients from those under ART was almost 94% in 2020, compared to 82.7% in 2016, and the increase is observed regardless of the ART regime. A shift towards integrase strand transfer inhibitors, with a higher efficacy, fewer adverse effects, and fewer drug interactions, is observed, which could contribute to the decrease in HIV transmission.

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