raltegravir-potassium and Weight-Gain

Integrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs.. NICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States.. Two hundred eighty-one women enrolled between 20 and 31 gestational weeks were randomized to raltegravir- or efavirenz-based cART and followed for ≥4 weeks. A low rate of weight gain was defined as <0.18 kg/wk and high as >0.59 kg/wk. We compared weight gain and BMI increase between treatment arms using Kruskal-Wallis tests. Logistic regression was used to investigate the association between weight gain and APOs.. Raltegravir-based cART was associated with significantly higher antepartum weight gain (median 0.36 kg/wk versus 0.29 kg/wk, P = 0.01) and BMI increase (median 0.14 kg/m 2 /wk versus 0.11 kg/m 2 /wk, P = 0.01) compared with efavirenz-based treatment. Women on raltegravir had less low weight gain (18% versus 36%) and more high weight gain (21% versus 12%) ( P = 0.001). Women with low weight gain were more likely than those with normal weight gain to have small for gestational age infants or a composite of APOs.. A raltegravir-based antiretroviral regimen was associated with significantly higher antepartum rate of weight gain and BMI increase compared with efavirenz-based treatment in antiretroviral-naive pregnant women.

Topics: Female; HIV Infections; Humans; Integrase Inhibitors; National Institute of Child Health and Human Development (U.S.); Pregnancy; Raltegravir Potassium; United States; Weight Gain

The adipokines leptin and adiponectin, produced primarily by adipose tissue, have diverse endocrine and immunologic effects, and circulating levels reflect adipocyte lipid content, local inflammation, and tissue composition. We assessed relationships between changes in regional fat depots, leptin and adiponectin levels, and metabolic and inflammatory markers over 96 weeks in the AIDS Clinical Trials Group (ACTG) A5260s metabolic substudy of the A5257 randomized trial of tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir among treatment-naive persons with human immunodeficiency virus (PWH).. Fat depots were measured using dual-energy absorptiometry and abdominal computed tomographic imaging at treatment initiation and 96 weeks later. Serum leptin and adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP) were measured at the same timepoints. Multivariable regression models assessed relationships between fat depots, adipokines, HOMA-IR, and hsCRP at week 96.. Two hundred thirty-four participants maintained viral suppression through 96 weeks (90% male, 29% black, median age 36 years). Serum leptin increased over 96 weeks (mean change 22%) while adiponectin did not (mean change 1%), which did not differ by study arm. Greater trunk, limb, and abdominal subcutaneous and visceral fat were associated with higher HOMA-IR and hsCRP at 96 weeks, but serum leptin level was a stronger determinant of these endpoints using a mediation model approach. A similar mediating effect was not observed for adiponectin.. Higher circulating leptin is associated with greater HOMA-IR and hsCRP independent of fat depot size, suggesting that greater adipocyte lipid content may contribute to impaired glucose tolerance and systemic inflammation among PWH starting antiretroviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Adipokines; Adult; Female; HIV Infections; Humans; Insulin Resistance; Male; Raltegravir Potassium; Weight Gain

Fat gain after antiretroviral therapy (ART) occurs, and its association with protease inhibitors (PIs) is unclear.. Peripheral and central fat depots and lean mass were measured using standardized and centrally read abdominal CT scans and whole-body dual-energy absorptiometry scans over a 96-week period in human immunodeficiency virus (HIV)-infected treatment-naive participants. The patients were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257. Within arm changes were assessed with signed-rank tests. The 96-week percentage changes in fat and lean mass in the 2 PI arms were not different, thus the PI arms were combined and compared to the RAL arm. Associations between baseline biomarkers and changes in body composition were assessed. All analyses used linear regression models.. 328 patients were randomized (90% male, 44% white non-Hispanic). The median age was 36 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 349 cells/μL. Overall, at week 96, increases in limb fat (13.4%), subcutaneous (19.9%) and visceral abdominal fat (25.8%), trunk fat (18%), and lean mass (1.8%) were apparent (P < .001 for changes within each arm). Changes for all fat and lean outcomes were not different between the PI arms or between the RAL and the combined PI arms. Higher baseline HIV-1 RNA levels were associated with greater gains in peripheral and central fat.. In treatment-naive participants initiating ART with TDF/FTC, no differences in lean mass and regional fat were found with RAL when compared with ATV/r or DRV/r over 96 weeks.. NCT00811954 and NCT00851799.

Topics: Abdominal Fat; Adult; Anti-HIV Agents; Body Composition; Female; HIV Infections; Humans; Male; Middle Aged; Protease Inhibitors; Raltegravir Potassium; RNA, Viral; Viral Load; Weight Gain

Topics: Dideoxynucleosides; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Insulin; Lamivudine; Menopause; Nitriles; Oxazines; Piperazines; Pyridones; Pyrimidines; Raltegravir Potassium; Waist Circumference; Weight Gain

Excessive weight gain has been reported with integrase strand transfer inhibitors (INSTIs). We evaluated weight changes in virologically suppressed adults with HIV who switched from non-INSTI regimens to raltegravir (RAL)-containing or dolutegravir (DTG)-containing antiretroviral therapy.. Retrospective single-centre cohort.. Adults who switched to RAL or DTG before or between January 2015 and October 2017 were identified. Virologically suppressed, treatment-experienced (≥2 years) individuals, at least 6 months on INSTI, with weight measurements 2 years or less pre and postswitch were included. Our analysis used a random effects model with linear slope pre and post-INSTI with adjustment for age, sex, ethnicity, preswitch-regimen (protease inhibitor vs. nonprotease inhibitor), and RAL vs. DTG use.. A total of 378 individuals, 81.2% male, 70.1% white ethnicity, median age of 49 years, median of four weight measurements per participant, and median weight and BMI at switch of 76.6 kg and 25.3 kg/m, respectively, were included. Weight increased by an average of 0.63 kg/year (95% confidence interval 0.17-1.09) preswitch with no overall change in rate of weight gain postswitch [+0.05 kg/year (-0.61-0.71, P = 0.88)]. In our adjusted model, a transition from minimal weight change to weight gain postswitch was isolated to older individuals though this lacked statistical significance [e.g., +1.59 kg/year (-0.26-3.45) if aged 65 years]. Our findings did not differ by sex, ethnicity, preswitch regimen, or RAL vs. DTG. Similar results were seen for BMI and after adjusting for fixed nucleoside/nucleotide reverse transcriptase inhibitor backbone.. We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically suppressed individuals.

Topics: Adult; Aged; Drug Substitution; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Raltegravir Potassium; Retrospective Studies; Sustained Virologic Response; Treatment Outcome; Weight Gain; Young Adult

: Integrase strand transfer inhibitor-based antiretroviral therapy can cause weight gain. It is unknown if this is a class effect, with limited data regarding raltegravir. In 37 virologically suppressed adults (36 men, mean age 49 years) who switched from tenofovir disoproxil fumarate to raltegravir 400 mg twice daily, mean weight changes from baseline at weeks 24, 48 and 96 were not significant (maximum 0.8 kg at week 24; all P ≥ 0.16). Weight gain may not occur with all integrase strand transfer inhibitors.

Topics: Adult; Anti-HIV Agents; Body Mass Index; Emtricitabine; HIV Infections; HIV-1; Humans; Male; Middle Aged; Raltegravir Potassium; Tenofovir; Weight Gain