scholarly journals Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy

2019 ◽  
Vol 70 (7) ◽  
pp. 1267-1274 ◽  
Author(s):  
Kassem Bourgi ◽  
Peter F Rebeiro ◽  
Megan Turner ◽  
Jessica L Castilho ◽  
Todd Hulgan ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Transcriptase Inhibitor ◽  
Virologic Suppression ◽  
Strand Transfer ◽  
Care Clinic ◽  
Art Initiation ◽  
Treatment Naïve ◽  
Transfer Inhibitor ◽  
Restricted Cubic Splines

Abstract Background Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)–based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. Methods Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)–, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. Results Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. Conclusions Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.

scholarly journals 881. Long-term Weight Gain After Initiating Combination Antiretroviral Therapy in Treatment-naïve Asian People Living with HIV

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S532-S533
Author(s):  
Naokatsu Ando ◽  
Takeshi Nishijima ◽  
Daisuke Mizushima ◽  
Yosuke Inaba ◽  
Yohei Kawasaki ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Transcriptase Inhibitor ◽  
People Living With Hiv ◽  
Strand Transfer ◽  
Clinical Issue ◽  
Asian Populations ◽  
Asian Patients ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide

Abstract Background Weight gain after the initiation of antiretroviral therapy (ART) is becoming a major clinical issue in treatment-naïve people living with human immunodeficiency virus (PLWH). However, limited data exist for the Asian populations. We aimed to investigate changes in weight after the initiation of ART therapy in treatment-naïve Asian patients. Methods We evaluated adult, treatment-naïve Asian PLWH who started integrase strand transfer inhibitor (INSTI)-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART at AIDS Clinical Center, Tokyo, between January 2005 and February 2019. They were followed up until October 2019. Multivariate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight by ART class (INSTI, PI, and NNRTI), each key drug (dolutegravir [DTG], elvitegravir [EVG], raltegravir [RAL], and darunavir [DRV]), and each key drug with or without the use of tenofovir alafenamide (TAF)/emtricitabine (FTC) was reported at 3-month intervals until censoring or 5 years. Results Among the 1,579 study patients, 610 (38.6%), 929 (58.8%), and 40 (2.5%) started INSTI-, PI-, and NNRTI-based ART. After 5 years, PLWH who initiated DTG- (5.3 kg), DRV- (4.0 kg), and EVG-based treatment (4.6 kg) gained more weight than those who initiated RAL-based treatment (1.8 kg). PLWH who initiated DTG plus TAF/FTC (6.7 kg) gained the largest weight. Conclusion In the Asian PLWH population, ART-associated weight gain continues to increase for 5 years after treatment initiation. DTG plus TAF/FTC was associated with the largest weight gain. Disclosures All Authors: No reported disclosures

Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir

Infection ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Leonardo Calza ◽  
Vincenzo Colangeli ◽  
Marco Borderi ◽  
Isabella Bon ◽  
Aurora Borioni ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

scholarly journals 334. Weight Change Associated with Antiretroviral Therapy Switch to Integrase Strand Transfer Inhibitor-Based Regimens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S177-S177 ◽  
Author(s):  
Saghar Saber ◽  
Andrew B Bernstein ◽  
Andrew D Sparks ◽  
Marc O Siegel
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Weight Change ◽  
Statistical Significance ◽  
Inverse Correlation ◽  
Cd4 Count ◽  
Strand Transfer ◽  
Significant Difference ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Background An association between switching antiretroviral therapy (ART) to integrase strand transfer inhibitor (INSTI)-based ART and weight gain has been previously reported. However, insufficient data exists on risk factors associated with such weight gain. Methods We reviewed charts of 119 virally-suppressed HIV-positive patients switched from nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based ART to INSTI-based ART and compared their weight change over 17 months to 56 virally-suppressed patients who were maintained on NNRTI-based regimens over the same period.We looked at variables associated with weight gain including age, weight, body mass index (BMI), gender, CD4 count, starting ART, and final INSTI-based ART. Results The 119 patients switched to INSTI-based ART gained an average of 6.9 lbs compared with an average 1 lbs weight gain in the 56 patients who were maintained on NNRTI-based ART (P = 0.002). There was also a statistically significant difference in the percentage % weight change between the two groups (4.2% vs. 0.7%, P < 0.001).There was an average 1.2 lbs weight loss in 92 of the 119 patients with weights recorded 17 months before switching ART, compared with an average 6.7 lbs weight gain after the switch (P < 0.001).There was no association between gender, CD4 count at the time of switch, starting ART, or final INSTI-based ART with weight gain. However, patients weighing < 150 lbs at the time of switch had a greater % weight gain than patients weighing >200 lbs (6.9% vs. 2.7%, P = 0.02) and a trend to greater % weight gain than those weighing ≥150 to ≤ 200 lbs (6.9% vs. 3.8%, P = 0.06). There was marginal statistical significance when comparing those with BMIs < 25 to those with BMIs ≥25 to ≤ 30 (8.2 vs. 6.5 lbs, P = 0.069) and those with BMIs >30 (8.2 vs. 5.0 lbs, P = 0.057). There was an inverse correlation between age and weight gain, indicating that less weight was gained when switching to INSTI-based ART as the age of the patient increased (ρ = -0.211, P = 0.021). Conclusion Our study showed a statistically significant weight gain in patients switched from NNRTI- or PI- to INSTI-based ART compared with patients maintained on NNRTI-based ART.Baseline variables associated with greater weight gain included weight <150 lbs, BMI <25 and younger age. Disclosures All authors: No reported disclosures.

scholarly journals Persistent Low-level Viremia While on Antiretroviral Therapy Is an Independent Risk Factor for Virologic Failure

2019 ◽  
Vol 69 (12) ◽  
pp. 2145-2152 ◽  
Author(s):  
Christie Joya ◽  
Seung Hyun Won ◽  
Christina Schofield ◽  
Tahaniyat Lalani ◽  
Ryan C Maves ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Proportional Hazards ◽  
Limit Of Detection ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Cox Proportional Hazards ◽  
The Body ◽  
Strand Transfer ◽  
Low Level ◽  
Art Initiation

Abstract Background Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. Methods NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50–199 copies/mL on <25% of measurements), pLLV (VL of 50–199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200–1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. Results Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42–4.93]), and hLV (2.29 [1.78–2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06–1.68]) and antiretroviral use prior to ART (1.79 [1.34–2.38]). Older age at ART initiation (0.71 [0.61–0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51–0.90]) or integrase strand transfer inhibitor use (0.26 [0.13–0.53]) were protective. Conclusion Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.

scholarly journals Comparison of Time to Viral Suppression Among Treatment-Naïve HIV-Infected Adults Initiating Combination Antiretroviral Therapy by Antiretroviral Regimen Class

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S432-S432
Author(s):  
Karen Jacobson ◽  
Onyema Ogbuagu
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Median Time ◽  
Viral Suppression ◽  
Limit Of Detection ◽  
Baseline Viral Load ◽  
Virologic Suppression ◽  
Hiv Patients ◽  
Art Initiation ◽  
Treatment Naïve

Abstract Background Antiretroviral therapy (ART) regimens for the treatment of HIV that incorporate the integrase strand inhibitor (INSTI) class of antiretroviral medications have high efficacy and tolerability, and may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in viral suppression are not well-defined in routine clinical settings. Methods We performed a retrospective single-center chart review of treatment-naïve HIV patients initiating ART between 2013 and 2016. Among patients on different ART regimen types, we compared rates of achievement of viral suppression (defined as viral load less than limit of detection or &lt;20 copies/uL) over time and median time to viral suppression using chi-square and independent samples median testing. Patients who were prescribed nonstandard regimens, were nonadherent, or discontinued or changed ART within 6 months were excluded. Results One hundred and fifty-five patients—45 (29.0%) female and 110 (71%) male—met study inclusion criteria. Mean age at ART initiation was 41.3 years (SD 12.5), and mean baseline viral load was 293,974 copies/uL. Twelve (7.7%) patients had an opportunistic infection diagnosed at time of ART initiation. Seventy-one (45.8%) initiated an INSTI-based ART regimen, 58 (37.4%) initiated a NNRTI-based regimen, and 26 (16.8%) initiated a PI-based regimen. Eighty-one (52.3%) patients had documented viral suppression, with median time to viral suppression 105 days (IQR 49–159). Patients on INSTI regimens were more likely to achieve viral suppression by 6 months (93.2% compared with 69.7% on NNRTIs and 30.8% on PIs), and had lower median time to suppression (62.6 days vs. 140.5 days on NNRTI regimens and 154.5 days on PI regimens, P = 0.002). Conclusion In this cohort, patients on INSTI-based ART regimens experienced higher rates of viral suppression at 6 months and shorter time from ART initiation to viral suppression. In HIV patients on INSTI-based ART regimens, virologic failure should be suspected prior to the current recommendation of 6 months. Disclosures All authors: No reported disclosures.

scholarly journals Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Rima K. Acosta ◽  
Madeleine Willkom ◽  
Ross Martin ◽  
Silvia Chang ◽  
Xuelian Wei ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Virologic Suppression ◽  
Strand Transfer ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Inhibitor Resistance ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

ABSTRACT In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.7% nucleoside reverse transcriptase inhibitor resistance (NRTI-R), 14.1% nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R), and 3.5% protease inhibitor resistance (PI-R) in the 1,274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.

scholarly journals 893. Evaluating Weight Gain in Treatment-naïve, HIV-infected Patients Started on Antiretroviral Therapy

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S538-S538
Author(s):  
Nimra Chaudhry ◽  
Eris Cani ◽  
Lendelle Raymond ◽  
Tae Park ◽  
Timothy Kanter
Keyword(s):  
Weight Gain ◽  
Primary Objective ◽  
Average Weight ◽  
City Hospital ◽  
Strand Transfer ◽  
Art Initiation ◽  
Average Change ◽  
Treatment Naïve ◽  
The Difference ◽  
Tenofovir Alafenamide

Abstract Background There is increasing evidence that integrase strand transfer inhibitors (INSTIs) are associated with more weight gain when compared to other antiretroviral (ART) classes. Thus, the primary objective of the study was to evaluate the difference in weight gain at 6 and 18 months among treatment-naïve patients started on an INSTI-based versus a non-INSTI-based ART regimen. Methods This was a retrospective cohort study of ART-naive adults who were initiated and maintained on INSTI and non-INSTI based regimens for at least 18 months at an HIV clinic in an inner-city hospital from January 2013 to June 2019. The non-INSTI-based regimens were darunavir (DRV) or rilpivirine (RPV)-based. Data collected included patient demographics, ART regimen, pre- and post-ART initiation weight in kilograms (kg), body mass index (BMI), CD4 count, and viral load. A two-tailed t-test was used to compare change in weight in INSTI-based versus non-INSTI-based regimens. Sub-group analyses were conducted using the ANOVA test. Results Out of 170 patients, 60% were initiated on an INSTI-based regimen, 7.1% on a DRV-based regimen, and 32.9% on a RPV-based regimen. Of the patients initiated on INSTI-based regimens, 73.5% were on elvitegravir (EVG),16.7% on dolutegravir, 8.8% on bictegravir, and 0.98% on raltegravir. The mean age at ART initiation was 38 years with majority of the patients described as Black. More male patients received an INSTI-based regimen compared to females (77.5% vs. 32%). The average change in weight at 6 and 18 months in the INSTI-based group vs non-INSTI-based group was +3.6 kg vs. +2.9 kg (95% CI -2.2-0.7, p=0.317) and +5.7 kg vs.+4.8 kg (95% CI -3.2-1.2, p=0.357) respectively. There was no significant average change in weight among the INSTI-based regimens (+3.6 kg), vs DRV (+5.3 kg), or RPV (+2.4 kg) based regimens at 6 months (p=0.108) and 18 months [(+5.7 kg) vs (+7.2 kg), vs (+4.3 kg) (p=0.186) respectively]. Among the INSTIs, EVG was associated with the highest increase in weight at both 6 and 18 months (+3.9 kg and +5.8 kg). Forty-six percent of patients in the INSTI group were on tenofovir alafenamide (TAF) while no patients received TAF in the non-INSTI groups. Conclusion When comparing INSTI-based to DRV or RPV-based regimens, there was no significant increase in average weight at 6 and 18 months. Disclosures All Authors: No reported disclosures

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

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 &lt; 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

scholarly journals Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mayumi Imahashi ◽  
Hirotaka Ode ◽  
Ayumi Kobayashi ◽  
Michiko Nemoto ◽  
Masakazu Matsuda ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Intestinal Dysbiosis ◽  
Α Diversity ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

AbstractIn HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy

2011 ◽  
Vol 16 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Benjamin Young ◽  
Signe Fransen ◽  
Kenneth S Greenberg ◽  
Amy Thomas ◽  
Sharon Martens ◽  
...  
Keyword(s):  
Case Report ◽  
Antiretroviral Therapy ◽  
Multidrug Resistant ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1
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