Real-World Assessment of Weight Change in African American Females and Hispanics with HIV-1 After Initiating Integrase Strand-Transfer Inhibitors or Protease Inhibitors

Background: Studies have shown an increase in weight among people living with human immunodeficiency virus (PLWH) who have also initiated integrase strand transfer inhibitors (INSTI). However, limited data are available regarding comparison of these changes with other antiretroviral regimens. Objective: To assess differences in weight gain after initiating INSTI- versus protease inhibitor (PI)- based regimens among treatment-naïve PLWH overall, and among a subpopulation of females only. Methods: This retrospective, observational cohort study included data from the Optum® deidentified Electronic Health Record (EHR) database. Adult PLWH who initiated INSTI- or PI-based regimens between March 1, 2016 and June 30, 2018 (index date was the first INSTI or PI prescription in this period) with ≥12-month baseline and follow-up periods, ≥1 weight measure during each period, and no prior antiretroviral use were included. The last weight measure between 12 months pre- and 30 days post-index was defined as baseline weight; the last measure between the months 4 and 12 of follow-up was defined as post-weight. Weight change was reported as absolute change and proportion of patients with increased weight. Cohorts were balanced using propensity score (PS) matching. Multivariable models were used to compare outcomes of interest. Results: After matching, 1588 patients were included (794 per cohort). At baseline, 46% were <50 years old, 26% were females, 12% had Type II diabetes and 30% had hypertension (mean baseline weight: INSTI: 83 kg (183 lb), PI: 82 kg (181 lb); P = 0.3). The mean time to follow-up weight measure was 9.3 months; INSTI initiators had a 1.3 kg (2.9 lb) greater mean weight gain (95% CI: 0.5–2.0), and a higher proportion with ≥5% weight gain (30.7% vs 26.1%; [OR=1.3, 95% CI: 1.0–1.6]) than PI initiators. Differences in weight gain between regimens were larger among females; female INSTI initiators had a 2.5 kg (5.3 lb) greater mean weight gain (95% CI: 0.7–4.2) and a higher proportion with ≥5% weight gain (37.5% vs 26.4%; OR=1.7; 95% CI [1.1–2.6]) than PI initiators. Conclusion: In a real-world setting, compared to PI-based regimens, INSTI-based regimens are associated with greater weight gain for treatment-naïve PLWH. This study may inform HIV treatment choice for health care providers.

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1043. The impact of integrase strand transfer inhibitors (InSTIs) on weight gain among adults with HIV in clinical care

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1229 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S551-S551

Author(s):

Sneha Thatipelli ◽

Chad Achenbach ◽

Shannon Galvin

Keyword(s):

Weight Gain ◽

Weight Change ◽

Metabolic Diseases ◽

Clinical Care ◽

First Year ◽

Strand Transfer ◽

Art Initiation ◽

Integrase Strand Transfer Inhibitors ◽

Clinically Significant ◽

The Impact

Abstract Background Integrase strand transfer inhibitors (InSTIs) as ART for HIV has been associated with clinically significant weight gain, in addition to the “return to health phenomenon”. Methods We conducted a cohort study on adults over 18 with HIV, who had baseline weights and an additional weight at least 6 months later. Individuals with malignancies, thyroid disorders, and disseminated tuberculosis or mycobacterium avium complex were excluded. To understand the impact of InSTIs on chronic vs. recently infected persons, we divided the cohort into four groups: (1) well-controlled on non-InSTI ART [WN] (2) well-controlled on InSTI ART [WI] (3) uncontrolled on non-InSTI ART [UN], and (4) uncontrolled on InSTI ART [UI]. Well-controlled persons (viral load < 2000) were proxies for chronic infection on long-term ART and uncontrolled for recently infected and initiated on ART. New diagnoses of diabetes, hyperlipidemia, and hypertension were determined by ICD10 codes. Participants with a weight change more than 10 kg in 6 months were excluded. Results 612 of the initial 910 participants in the cohort met the inclusion criteria. Comparing those who remained on the designated regimen throughout the study led to 86 WN, 153 WI, 166 UN, and 145 UI. Mean weight change at 6 months for WN was +0.22 kg (95% CI [-0.86, 1.3]), at 1 year was -0.86 kg (95% CI [-2.94, 1.22]), and at 2 years was +0.026 kg (95% CI [-2.347, 2.399]). For WI, mean weight change at 6 months was +0.21 kg (95% CI [-0.79, 1.21]), at 1 year was -0.50 kg (95% CI [-2.02, 1.04]), and at 2 years was +0.43 kg (95% CI [-1.35, 2.21]). UN gained weight until the first year (+1.74 kg at 6 mo (95% CI [0.24, 3.24]) and +3.84 kg at 1 year (95% CI [1.57, 6.11])), but plateaued at 2 years (+2.42 kg (95% CI [-0.44, 5.28])). At 6 months mean weight gain for UI was +0.78 kg (95% CI [-0.15, 1.71]), at 1 year was +2.33 kg (95% CI [1.02, 3.64]), and at 2 years was +3.04 kg (95% CI [1.2, 4.85]). WI had a higher incidence of diabetes (37% vs. 32%, p=0.40), hyperlipidemia (32% vs. 29%, p=0.66), and hypertension (34% vs. 26%, p=0.19) compared to WN. Conclusion InSTIs may confer a larger and more sustained weight gain among individuals in the first two years after ART initiation. Well controlled individuals did not have statistically significant weight change, but those on Insti-based ART had more metabolic diseases. Disclosures All Authors: No reported disclosures

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Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection

Scientific Reports ◽

10.1038/s41598-021-90678-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Prats ◽

Ignacio Martínez-Zalacaín ◽

Beatriz Mothe ◽

Eugènia Negredo ◽

Núria Pérez-Álvarez ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Integrase Inhibitor ◽

Strand Transfer ◽

Cognitive Differences ◽

Integrase Strand Transfer Inhibitors ◽

Initiation Of Therapy ◽

Main Component ◽

Living With Hiv ◽

The Impact ◽

Hiv 1

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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Susceptibility to HIV-1 integrase strand transfer inhibitors (INSTIs) in highly treatment-experienced patients who failed an INSTI-based regimen

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2020.106027 ◽

2020 ◽

Vol 56 (1) ◽

pp. 106027

Author(s):

Maria M. Santoro ◽

Chiara Fornabaio ◽

Marina Malena ◽

Laura Galli ◽

Andrea Poli ◽

...

Keyword(s):

Strand Transfer ◽

Integrase Strand Transfer Inhibitors ◽

Hiv 1

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Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients

HIV Clinical Trials ◽

10.1080/15284336.2016.1153303 ◽

2016 ◽

Vol 17 (3) ◽

pp. 109-113 ◽

Cited By ~ 5

Author(s):

M. Sayan ◽

A. Gündüz ◽

G. Ersöz ◽

A. İnan ◽

A. Deveci ◽

...

Keyword(s):

Strand Transfer ◽

Resistance Mutations ◽

Integrase Strand Transfer Inhibitors ◽

Turkish Patients ◽

Hiv 1

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Heterocycle amide isosteres: An approach to overcoming resistance for HIV-1 integrase strand transfer inhibitors

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2019.126784 ◽

2020 ◽

Vol 30 (3) ◽

pp. 126784 ◽

Cited By ~ 1

Author(s):

Kevin M. Peese ◽

B. Narasimhulu Naidu ◽

Manoj Patel ◽

Chen Li ◽

David R. Langley ◽

...

Keyword(s):

Strand Transfer ◽

Integrase Strand Transfer Inhibitors ◽

Hiv 1

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Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors

Clinical Pharmacokinetics ◽

10.1007/s40262-016-0424-1 ◽

2016 ◽

Vol 56 (1) ◽

pp. 25-40 ◽

Cited By ~ 50

Author(s):

Anthony T. Podany ◽

Kimberly K. Scarsi ◽

Courtney V. Fletcher

Keyword(s):

Strand Transfer ◽

Pharmacokinetics And Pharmacodynamics ◽

Clinical Pharmacokinetics ◽

Integrase Strand Transfer Inhibitors ◽

Hiv 1

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Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa349 ◽

2020 ◽

Vol 75 (12) ◽

pp. 3517-3524

Author(s):

M Casadellà ◽

J R Santos ◽

M Noguera-Julian ◽

R Micán-Rivera ◽

P Domingo ◽

...

Keyword(s):

Reverse Transcriptase ◽

Low Frequency ◽

Transmitted Drug Resistance ◽

Strand Transfer ◽

Resistance Mutations ◽

First Line ◽

Primary Resistance ◽

Integrase Strand Transfer Inhibitors ◽

Virological Outcomes ◽

Hiv 1

Abstract Background Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. Objectives We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. Methods Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%–19% of the virus population were considered to be low-frequency variants. Results From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. Conclusions Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.

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