Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide discontinuation and return to normal weight

2020 ◽  
pp. 095646242096434 ◽  
Author(s):  
Blake Max ◽  
Patricia DeMarais

HIV integrase strand transfer inhibitors (INSTI) are considered well tolerated with few treatment-limiting adverse effects. However, emerging data from clinical trials has identified excessive weight gain possibly due to INSTI alone or with tenofovir alafenamide as a new and possible long-term complication of combination antiretroviral therapy (cART). Identifying who is at greatest risk and whether the unintended weight gain is reversible remain unanswered questions. We report a return to baseline weight after switching back to tenofovir disoproxil/emtricitabine/efavirenz (Atripla®) in a woman who had profound weight gain due to tenofovir alafenamide/emtricitabine/cobicistat/elvitegravir (Genvoya®).

Author(s):  
Yen-Wen Chen ◽  
Helene Hardy ◽  
Christopher D. Pericone ◽  
Wing Chow

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.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S551-S551
Author(s):  
Sneha Thatipelli ◽  
Chad Achenbach ◽  
Shannon Galvin

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


2019 ◽  
Author(s):  
Hanqing Chen ◽  
Suhua Zou ◽  
Zhuyu Li ◽  
Jianbo Yang ◽  
Jian Cai ◽  
...  

Abstract Background Pre-pregnancy body mass index and gestational weight gain were related to perinatal outcomes. It was not know the changes of pre-pregnancy body mass index, weight gain during pregnancy and its effect on perinatal outcomes in two-child women.Methods This was a retrospective study. Data of single term women delivered in the First Affiliated Hospital of Sun Yat-sen University were collected from July 2017 to June 2018. Gestational weight gain criteria of the American Institute of Medical Research and pre-pregnancy body mass index classes were used to evaluate the effects on pregnancy outcomes.Results A total of 3049 cases were enrolled in the study. Overweight cases was 9.0% and obesity was 2.4%. The weight gain of the two-child women was less than that of primipara(12.4±3.9vs13.3±4.0kg, P<0.001). The proportion of primipara with excessive weight gain was higher compared to two-child women(20.1%versus17.3%, P<0.001). There were 40.0% overweight primipara and 55.2% of two-child women had excessive weight gain. And 40.5% primipara and 54.5% two-child women of obesity had excessive weight gain during pregnancy. Obese primipara increased the risk of pre-eclampsia (aOR2.38, 95%CI 0.76-7.46). And the odds of diabetes mellitus and large for gestational age also increased in this group (aOR3.49, 95%CI 1.46-8.35 and aOR7.65, 95%CI 1.83-31.97, respectively). Two-child women had similar results. Underweight primipara with excessive weight gain increased the pre-eclampsia risk (aOR2.26, 95%CI 0.29-17.46). Normal weight and overweight/obese primipara also had similar results. But in two-child women, only overweight/obesity increased the risk of pre-eclampsia (aOR2.01, 95%CI 0.41-9.98). Underweight two-child women with less weight gain increased the risk of diabetes(aOR2.06, 95%CI 0.43-9.8). Two-child women with overweight/obese increased the odds of LGA even if they had less weight gain(aOR2.58, 95%CI 0.11-63.22). Normal weight primipara and two-child women with overweight and obese with excessive weight gain had similar results. On the other way, underweight primipara with less weight gain increased the risk of SGA(aOR1.74, 95%CI 0.81-3.76).Conclusions Gestational weight gain of two-child women was less than primipara. Overweight/obese women with excessive weight gain of two-child women increased the risk of adverse outcomes.


2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Lucia Taramasso ◽  
Paolo Bonfanti ◽  
Elena Ricci ◽  
Giancarlo Orofino ◽  
Nicola Squillace ◽  
...  

Abstract Background An unexpected excess in weight gain has recently been reported in the course of dolutegravir (DTG) treatment. The aim of the present study was to investigate whether weight gain differs among different DTG-containing regimens. Methods Adult naïve and experienced people with HIV (PWH) initiating DTG-based antiretroviral therapy (ART) between July 2014 and December 2019 in the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) prospective cohort were included. We used an adjusted general linear model to compare weight change among backbone groups and a Cox proportional hazard regression model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for weight increases &gt;10% from baseline. Results A total of 713 participants, 25.3% women and 91% Caucasian, were included. Of these, 195 (27.4%) started DTG as their first ART regimen, whereas 518 (72.6%) were ART-experienced. DTG was associated with abacavir/lamivudine in 326 participants, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 148, boosted protease inhibitors in 60, rilpivirine in 45, lamivudine in 75, and tenofovir alafenamide (TAF)/FTC in 59. At 6 and 12 months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG. Baseline CD4 &lt;200 cells/mm3 (HR, 1.84; 95% CI, 1.15 to 2.96), being ART-naïve (HR, 2.24; 95% CI, 1.24 to 4.18), and treatment with TDF/FTC+DTG (HR, 1.92; 95% CI, 1.23 to 2.98) or TAF/FTC+DTG (HR, 3.80; 95% CI, 1.75 to 8.23) were associated with weight gain &gt;10% from baseline. Higher weight (HR, 0.97 by 1 kg; 95% CI, 0.96 to 0.99) and female gender (HR, 0.54; 95% CI, 0.33 to 0.88) were protective against weight gain. Conclusions Naïve PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones were at higher risk of weight increase in the course of DTG-based ART.


Biochemistry ◽  
2008 ◽  
Vol 47 (51) ◽  
pp. 13481-13488 ◽  
Author(s):  
David R. Langley ◽  
Himadri K. Samanta ◽  
Zeyu Lin ◽  
Michael A. Walker ◽  
Mark R. Krystal ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1290 ◽  
Author(s):  
Melanie Larsson ◽  
Mads Lind ◽  
Anni Larnkjær ◽  
Anette Due ◽  
Irina Blom ◽  
...  

Some infants experience excessive weight gain (EWG) during exclusive breastfeeding, but causes and consequences are unknown. The objective was to identify factors associated with early EWG. Infants with EWG (HW-group) were examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight gain (NW-group). Anthropometry, body composition, milk and blood samples, and milk intake were measured. Mean body-mass-index-for-age z-scores (BAZ) increased 1.93 from birth to 5 mo in the HW-group (n = 13) while the NW-group (n = 17) was unchanged (−0.01). The HW-group had 70% more fat mass at 5 mo, and then showed marked catch-down in BAZ from 5 to 18 mo (−0.84). Milk intake at 5–6 mo did not differ between the groups. In the HW-group milk-leptin was lower at 5 mo and serum-leptin was considerably higher at 5 and 9 mo compared to the NW-group. Serum-leptin at 5 mo was positively associated with weight-for-age z-score (WAZ) and fat mass and negatively with WAZ change from 5 to 9 mo. In conclusion, breastfed infants with EWG had catch-down growth when other foods were introduced. Low milk-leptin in the HW-group may have stimulated appetite and milk intake when weight gain was high. High serum-leptin in the HW-group suggests early leptin resistance, which could impact cerebral regulation of energy intake. Larger studies are needed to confirm these results.


Author(s):  
J Li ◽  
E H Yusuf ◽  
A L Agwu

Abstract Children with perinatally acquired human immunodeficiency virus (PHIV) face a lifetime of combination antiretroviral treatment that often includes dolutegravir (DTG). DTG, an integrase strand inhibitor that has been linked to weight gain in adults, is increasingly being used in children. Understanding its potential short- and long-term sequelae in children is critically important. We report a case of excessive weight gain in a child with PHIV on DTG and provide a brief literature review.


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