Dtg And Weight Gain

1y ago
8 Views
2 Downloads
3.90 MB
40 Pages
Last View : 18d ago
Last Download : 2m ago
Upload by : Duke Fulford
Transcription

DTG AND WEIGHT GAINDr Bronwyn BoschEzintsha19 Nov 2020

DECLARATIONS Grants from USAID, Unitaid, South African Medical Research Council(SAMRC) and ViiV Healthcare during conduct of clinical trials Non-financial support from ViiV Healthcare, Gilead Sciences and MSD duringconduct of clinical trials Honoraria and speakers’ fees received from Cipla

OUTLINENew ART Guidelines (SA)DolutegravirART and weight gainProposed weight gain theoriesInterventions and treatment optionsReferencesPresenter contact details

2019 ART GUIDELINESGoals of ART: Decrease HIV-related conditions, including OI’s Minimize development of treatment resistance Decrease morbidity and mortality from HIV/AIDS Improve patients’ QoLEligibility: All PLWH (regardless of age, CD4, clinical stage) Ideally: initiate on same day / within 7 days Prioritized for rapid initiation: pregnant women, infants, children( 5 y/o), those with advanced HIVWhat’s new: DTG (role in 1st, 2nd and 3rd line regimens)SA NDoH ART Guidelines. 2019

2019 ART GUIDELINES.Adults on 1st lineARTVL within last 6 months 50Counsel on DTGSwitch50 - 999Declines switchOriginal regimenTDF XTC EFV/NVPAZT/ABC 3TC EFV/NVPNew ARTTDF XTC DTGAZT/ABC 3TC DTGStay on currentARTSwitch 1000Declines switchTDF XTC EFV/NVPAZT/ABC 3TC EFV/NVPTDF XTC DTGAZT/ABC 3TC DTGStay on currentARTAdherence support if repeat VL(3months) 1000NNRTI-basedInSTI / PI-basedConsider 2nd lineRequires 3 VL 1000 before aswitch (over 2yrs)OR 2 VL 1000with signs ofimmunological /clinical failureSA NDoH ART Guidelines. 2019

INTEGRASE STRANDINHIBITORS Prevent transfer of pro-viral DNA strands into host chromosomal DNA Integrase inhibitors (InSTIs) “-gravir" Dolutegravir (DTG), raltegravir (RAL), elvitegravir, bictegravir, cabotegravir DTG preferred over RAL: because of barrier to resistance, daily dosing and availabilityin FDC Generally well tolerated: S/e commonly mild and rarely lead to discontinuation Insomnia – often eliminated by AM dosing DTG may increase serum creatinine (mild)o Does NOT represent renal damage and is not indication to switch to another drugWeight gainAtta, M. Clinical Pharmacology in HIV Therapy, CJASN March2019, 14 (3) 435-444.

Usual dose: 50mg ODDOLUTEGRAVIR(DTG) Taken with / without food, With a meal increases drug levels (esp high fat meal) Benefits:ARTexperienced Well tolerated High genetic barrier to resistance Concerns: Weight gainTANGO NTD’sDAWNING Drug-drug interactions: supplements (calcium, magnesium, aluminum), antacids and multivitamins;STRIVINGART naïveSINGLESPRINGFLAMINGOGEMINIARIAmetformin; TB treatment. Efficacy proven in several RCT ART naïve and experienced patients Preference for EFV largely due to tolerability

DTG AND WEIGHTGAINPost approval side effect First noted 2018 InSTI class effect DTG RALAt risk groups: Women of African descent Use with TAF Patients with lower baseline CD4 counts and higher VLsThe Medical Biochemistry metabolic-and-clinical-consequences/

ART AND OBESITY: INSTIGreater after ART initiation than with switching / PrEP ”Return to health” “return to societal norm”HIVMany unknowns: OutliersTraditionalriskfactors Weight gain beyond 2 years Mechanisms Need clinical trials designed to look at weighto Preferably PrEP / switching trials to avoid return to health phenomenonART

OBESITYObesity BMI 30 kg/m2 Poor correlation with fat mass, but easy to measure No clear definitions on deleterious weight gain (geography, sex, race)Globally (2016):o13% of adults ( 650 million)o11% of men, 13% of womenoSA: 28.3% (2016)o40% overweight (BMI 25)Limited prevalence info for HIV adultshttps://gamapserver.who.int/gho/interactive charts/ncd/risk factors/obesity/atlas.htmlYitbarek et al, Diabetes Metab Syndr Obes 2020; Khatri et al, BMC Nutr 2020; Bourgi et al, J Int AIDS Soc 2020; Savinelli S et al, HIV Med 2020

OBESITYAdipose tissue confers risk depending on location: Visceral major risk factor for cardio-metabolic disease Subcutaneous fat neutral / protectiveAdipose depots expand in several ways: Hyperplasia (incr number) – “healthy” Hypertrophy (incr size) – dysfunctional, associated pathologiesChronic excessive caloric intake adipocyte dysfunction (triggers release of adipokines) chronic inflammation and insulin resistance adipose tissue fibrosis (impaired metabolic function) adipokines act directly on cardiovascular tissues & promote diseaseFuster, et al. Circ Res. 2016 May 27; 118(11): 1786–1807

HIV AND OBESITYBrain: strokes,dementiaHPTHeart: failure, IHDDMVascular disease,retinopathy, PN, CKDOACOMPLICATIONSMalignanciesKnees / hips / spineEndometrial, breast,ovarian, prostate, liver,gallbladder, kidney,colonFatigue, dementiaOSAFatty liver diseasePregnancyCarr, A. HIV and Obesity, Glasgow 2020.Liver failureMacrosomia, esity/how-obesity-affects-body

OBESITYSignificance: earlier deatho 5 kg/m2 BMI increase increases risk of death by 30%o Similar globallyo Suspected same risk in HIV adults as general populationConcern for metabolic effects As direct effect of InSTIoMETA-INSTI (metabolic adverse events following InSTI administration in spontaneous adverse event reports)oAnalysis of FDA AE Reporting System (FAERS) CVD risk is cumulative over many years (need long term data)

LESSONS FROM HISTORYYEARHIV LipodystrophyYEARHIV weight gain1996ART safe2014Modern ART safe1997Features reported, largely ignored2017Reports of generalized weight gain1998Syndrome recognized, linked to PIs2018Larger cohorts – INSTI linkRCT of DTG switching1999-2001Also linked to tNRTIsMechanism proposedPI switching 2019“TAF/DTG cause fat gain”“TDF/EFV prevent fat gain”2002Partially reversible with tNRTI switch2020 2003Prospective confirmationPrevented with initial TDF/ABC2004Rx: glitazones not very effectiveMany unknowns:- 3 drug classes?- Mechanisms?- Biology of risk factors?- Hierachy in drug classes?- Does weight gain stabilize?- Reversibility / treatment?- Clinical consequences?2005Mitochondrial mechanism2008PI (LPV/r) did NOT cause LD in RCTCarr, A. HIV and Obesity, Glasgow 2020.

ART AND OBESITYRandomised trialART-naïve: INSTIART-naïve: NNRTIART switchPrEPStudyTDF/F-3TCNEAT-001Spring-114891490 1.4ADVANCE 5.0FLAIRGEMINIDRIVETAF/FTCINSTIABC/3TCDRVr: 3.1EFV: 0 2.1 3.6 3.5, 3.9STEALTANGONEAT-022ATLASBRAAVEHPTN-077 0.7iPrExHPTN-083( 0.1) 0.3DISCOVER 0.5 2.4 8.0EFV: 2.0 1.3 3.1 2.1 2.4, 1.6Cont/Pbo 1.5DRVc: 1.8 1.9 0.8( 0.8) 1.8 0.9 1.1 0.8(PIr: 0.3) 0.3 0.2Pbo: 1.0(Pbo: 1.6) 1.3 1.7Carr, A. HIV and Obesity, Glasgow 2020.

MULTIVARIATE ANALYSIS OF WEIGHT GAIN FOLLOWING ARTINITIATION IN RCTS32* ** ** *** **1012 24 36 48 60 72 84 96Wks65BICDTGEVG/COBI43***** *** *****21012 24 36 48 60 72 84 96WksLS Mean Weight Δ, kg (95% CI)4INSTIPINNRTILS Mean Weight Δ, kg (95% CI)LS Mean Weight Δ, kg (95% CI)Pooled analysis of weight gain across 8 randomized phase III clinical trials of first-line ART initiationoccurring in 2003-2015 (N 5680)65TAFABCTDFZDV4**32*** ** *********1012 24 36 48 60 72 84 96Wks*Color-coded to match respective comparators, denoting P .05 vs NNRTI (first panel), EVG/COBI (second panel), or ZDV (last panel).Sax. Clin Infect Dis. 2020;71:1379.Slide credit: clinicaloptions.com

MULTIVARIATE ANALYSIS OF WEIGHT GAIN FOLLOWING ARTINITIATION IN RCTS Pooled analysis of weight gain 8 RCTs, ART initiation 2013 – 2015 5000 participants Results:o Weight gain greater in morerecent trialso Weight gain greater with newerART regimenso Demographic factors associatedwith weight gain similar to thoseseen elsewhereSax. Clin Infect Dis. 2020;71:1379.

TDF TAF COHORT:OPERAWeight change with switch from TDF to TAF(maintained other ARVs)Time to switch(months)INSTI(n 3281)NNRTI(n 1452)PIx(n 746)-60 to 00.420.660.310 to 92.642.251.989 0.290.20-0.11OPERA: Large longitudinal multisite cohort (US) All patients virally suppressed Switched TDF TAF switch non-InSTI anchor to InSTI Baseline BMI across arms 26-27Mallon. AIDS 2020. Abstr OAB0604.

TDF TAF COHORT:OPERAWeight change with switch from TDF to TAF (maintained other ARVs): InSTI AnchorsEstimated Weight Δ by TimeFrom TDF to TAF Switch, kg/yr(95% CI)EVG/c(n 2389)DTG(n 643)RAL(n 249)All INSTIs(n 3281)-60 to 0 mos0.71(0.53 to 0.90)0.73(0.34 to 1.11)-0.44(-0.79 to -0.08)0.42(0.26 to 0.59)0 to 9 mos2.51(2.05 to 2.96)2.38(1.64 to 3.13)1.80(0.57 to 3.03)2.64(2.26 to 3.01)9 mos0.36(0.12 to 0.61)-0.18(-0.64 to 0.28)0.63(-0.20 to 1.46)0.29(0.08 to 0.51)Conclusions: Switch to TAF associated with immediate increase in weight- Regardless of concomitant ARVs- Weight gain slowed / plateaued after 9 months Supports TAF as independent contributorMallon. AIDS 2020. Abstr OAB0604.

ADVANCE: DTG, TAF/TDF, EFV (NAÏVE)Mean change body weight: women RCT, Phase 3 (SA) 1053 participants DTG TAF/FTC vs DTG TDF/FTC vs EFV/TDF/FTCo Non-inferioro DTG better toleratedMean change body weight: menMean weight gain substantial: 96-week datao 7.1 kg in TAF/FTC DTG armo 4.3 kg in TDF/FTC DTG armo 2.3 kg in TDF/FTC/EFV arm Women menGriesel et al, AIDS 2020; Sokhela et al, AIDS 2020

ADVANCE: DTG, TAF/TDF, EFV (NAÏVE)BMI 628.430.129.129.2252015Sokhela et al, AIDS 2020; Mchiza et al, Int J Environ Res Public Health 2019Silverberg et al, AIDS 2020; LTC?lang en

NAMSAL DTG vs EFV 400mg ( TDF/3TC both) Phase 3, open-label, RCT in CameroonoOngoing 613 participants Weight gain greater in DTG arm (wk 96)oMedian weight gain 5.0kg (DTG)oVs median weight gain 3kg (EFV)Calmy et al. The Lancet 2020, Vol 7:10, E677-687

ARIAATV/r DTG/ABC/3TCTDF/FTC(N 248)(N 247)Age, median (range), y37.5 (19-79)37.0 (20-65)102 (41)108 (44)White115 (46)107 (43)Asian22 (9)23 (9)Race, n (%)African American/Africanheritage DTG/ABC/3TC (superior) vs ATV/r TDF/FTC Phase 3b, 495 participantsHIV-1 RNA, mean, log10 c/mL4.484.44 Participants from 12 countries (SA n 66)HIV-1 RNA 100,000 c/mL, n(%)69 (28)66 (27) Treatment naïve female adultsCD4 cell count, mean,cells/mm3370380 48 weeksCD4 cell count 350 cells/mm3,n (%)130 (52)123 (50) Retrospective review on weights: only taken atWeight, mean (SD), kg70.1 (19.3)71.8 (21.0)(SD), kg/m226.8 (6.9)27.3 (7.4)baseline, but sent to lab for eGFR calculation23rd International AIDS Conference; July 6-10, 2020; VirtualBMI, meanWalmsley et al. AIDS 2020: Virtual. Poster PEB0233

ARIA Baseline characteristics associated with 10% weightgaino DTG regimeno Black participanto Elevated baseline VLo Low baseline CD4 counts Long term data:o Rate of weight increase moderated after 1 year onDTG23rd International AIDS Conference; July 6-10, 2020; VirtualWalmsley et al. AIDS 2020: Virtual. Poster PEB0233

NA-ACCORDINSTIn 4,093PIn 7,063NNRTIn 10,711 Adult, PLWH (ART naïve) Initiating InSTI, PI or NNRTI-based ART (US) Jan 2007 – Dec 2016 22972 participants InSTI: mean estimated weight 5.9 kg (5-year) Of those on InSTI:o Mean est 2-year weight change: 7.2kg (DTG)o Mean est 2-year weight change: 5.8kg (RAL)o Mean est 2-year weight change: 4.1kg (EVG)Bourgi et al, J Int AIDS Soc 2020

PREP STUDIES: TDF VS PLACEBO / TAFTDF/FTC vs Placebo (iPrEx)Difference fat lean massTAF/FTC vsTAF: 1.7kgTDF/FTC (DISCOVER)TDF: 0.5kg (significant)Glidden et al, Clin Infect Dis 2018; Ogbuago et al, CROI 2020 (abstract 92)

ADDITIONAL DATA ON WEIGHT GAIN AND ARTFROM RECENT CONFERENCESStudyPopulationReported OutcomeAFRICOS[1]Adults with HIV infection starting or switchingART at 12 PEPFAR supported clinics in Uganda,Kenya, Tanzania, and Nigeria(N 2927)1.85 times the rate of developing high BMI withDTG/3TC/TDF vs other ART; no significant difference inhyperglycemia incidence with DTG/3TC/TDF vs other ARTPooled analysis ofswitch toBIC/FTC/TAF[2]Virologically suppressed adults 65 yrs of agerandomized to switch to BIC/FTC/TAF in Study380-1844, Study 380-4030, Study 380-4449,and Study 380-1878 (N 140)Median weight gain of 1.0 kg (IQR: -0.9 to 3.0) at Wk 48Virologically suppressed adults on boosted DRVor ATV plus 2 NRTIs who switched toBIC/FTC/TAF in Study 380-1878 (N 533)Mean weight gain of 2.2 kg with switch to BIC/FTC/TAFwithout continuous increase after 48 wks; no different vscontinued background regimenBICSTaR[4]ART-naive and ART-experienced PWH startingBIC/FTC/TAF (N 513)Median weight gain at 12 mos: 2.5 kg in patients naive toART and 0.9 kg in ART-experienced patientsGEMINI-1 andGEMINI-2[5]ART-naive adults starting DTG 3TC (n 716)vs starting DTG TDF/FTC (n 717)Mean weight change from BL to Wk 144 was 3.7 kg withDTG 3TC vs 2.4 kg with DTG FTC/TDFLong-term follow-upof switch toBIC/FTC/TAF fromboosted PI[3]1. Ake. AIDS 2020. Abstr OAB0602. 2. Ramgopol. AIDS 2020. Abstr OAB0403. 3. Rockstroh. HIV Glasgow 2020. Abstr P037. 4. Spinner. HIVGlasgow 2020. Abstr P046. 5. Cahn. HIV Glasgow 2020. Abstr P018.Slide credit: clinicaloptions.com

Return to health phenomenon?Induced by InSTIs(possibly TAF)Inhibited by TDF (possibly EFV)WEIGHT GAINTHEORIESIncreased appetite / calorie intake?Reduced physical activity?More lipid storage?Improved "fat quality"?

WEIGHT GAIN THEORIES:RETURN TO HEALTH Link between weight gain and baseline low CD4 Advanced HIV disease weight loss & increased metabolic demandso Stopping viral replication lower energy requirements and weight gaino Alleviation of HIV-associated inflammation Hastens resolution of OI and GI dysfunctiono Improved appetite and nutrient absorption

WEIGHT GAIN THEORIES:INCREASED APPETITE Binding to MC4 receptor? InSTIs bind MC4R in vitro increased food consumption and increased adiposity Only affected at very high concentrationsMcMahon et al, PLoS ONE 2020

WEIGHT GAIN THEORIES:INHIBITED BY TDF, EFVOlder ARV’s (TDF, EFV) higher drug exposure Less weight gain (unclear mechanisms) ?GIT Sx ?lipoatrophyADVANCE: Extensive EFV metabolisers (CYP2B6 polymorphisms) similar weight gain to DTG Intermediate / slow metabolisers slower weight gainGriesel et al, AIDS 2020; Sokhela et al, AIDS 2020

WEIGHT GAIN THEORIES:A LTE RE D C A L O RI E I N TA KE M E TA B O LIC RATEWeightRestingmetabolicrate 30 PLWH (ART naïve) 53% DTG, 37% TAF Fasting RMR/V02, bodycomposition(calorimetry, DXA) Nutrient intake(dietician)Fat (kg)Calorieintake No significant changesin RMR or caloricintakeEckard et al, CROI 2020 (abstract 667)

WEIGHT GAIN THEORIES:RE D U CE D PH YSI C A L AC TI VI TYHIV adults with weight gain 5%: Observational cohort Mean age 54 y/o, 74% men switched to INSTI (n 118) no switch (n 163) Population attributable fractions (PAF’s) oflifestyle and InSTI regimens1. BMI2. CD4/CD8 ratio3. Physical activityGuaraldi et al, CROI 2020 (abstract 675)

WEIGHT GAIN THEORIES:I N STI -I NDUCE D A D I PO SE TI SSU E E F F E CT 14 macaques (noninfected) and 19 PLWH on ART Adipocyte size and fibrosiso Subcutaneous (SCAT) and visceral adipose tissue(VAT) Exposed adipose stem cells to DTG / RALo Elevated fibrosiso Increased adipocyte sizeo Greater lipid accumulationo Promotion of mitochondrial dysfunction and insulinresistance Limitations: all pts obese, cross-sectionalGorwood et al, Clin Infect Dis 2020 (in press)

WEIGHT GAIN THEORIES:IMPROVED FAT QUALITYObservational cohort in 418 PLWH who gained 5%weight on ART Modena HIV Metabolic Clinic (Italy) Those on InSTI had bigger jumps in BMI But decrease in visceral adipose tissue (therefore ?betterquality fat)Assessed fat quantity and quality Quantity: weight, total lean mass, total fat mass (DXA), CTmarkers (VAT, SAT EAT) Quality: VAT, SAT, EAT, L/S and psoas muscle density (CT scan) Fat density:o Lower fat density larger fat cells (adipocytes) incrfat contento Higher fat density greater inflammation and fibrosisGuaraldi et al, Glasgow 2020 (abstract O111)

INTERVENTIONSWHO population-level strategies:Physical inactivity 2010 Increase physical activityo 150mins exercise spread throughout the week Reduce intakeo Limit energy intake (fats and sugars)o No clear superior diet based on systematic review of specific dietsWHO, Global Action Plan 2013-2020, http://gamapserver.who.int/mapLibrary/

TREATMENT OPTIONSOther ART options:(To note: no evidence of reversal after switching) EFV-based regimens (NNRTI) Rilpivirine (RPV)-based regimens (NNRTI) oNot available in FDCoCannot be co-administered with Rif-based TB therapyoNot be started in patients with VL 100 000Newer agents: DOR, ISL, CabotegraviroCabotegravir (InSTI) not yet available in SAoHPTN studies (PrEP) – no significant weight gainCultural sensitivity: Underweight traditionally attracted stigma (HIV and TB) Overweight has connotations pertaining to wealth and statusEthical implications: Allow patients to make informed decisions Where clear harm over benefit (e.g. development of metabolicconsequences) HCW to use clinical discretion

THANK YOU!Questions?

REFERENCES1.Republic of South Africa National Department of Health. 2019 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy, Adolescents, Children, Infants and Neonates [Internet].[cited 2020 Nov 11]. Available from: https://sahivsoc.org/Files/2019 ART Guideline 28042020 pdf.pdf2.Yitbarek GY, Engidaw MT, Ayele BA, Tiruneh SA, Alamir MT. Magnitude of Obesity/Overweight and Its Associated Factors Among HIV/AIDS Patients on Antiretroviral Therapy in Jimma ZoneHospitals, SouthWest Ethiopia: Hospital-Based Cross-Sectional Study [Corrigendum]. Diabetes, Metab Syndr Obes Targets Ther [Internet]. 2020 May;Volume 13:1619–20. Available --peer-reviewed-article-DMSO3.Khatri S, Amatya A, Shrestha B. Nutritional status and the associated factors among people living with HIV: an evidence from cross-sectional survey in hospital based antiretroviral therapy site inKathmandu, Nepal. BMC Nutr [Internet]. 2020 Dec 15;6(1):22. Available from: /s40795-020-00346-74.Bourgi K, Jenkins CA, Rebeiro PF, Shepherd BE, Palella F, Moore RD, et al. Weight gain among treatment‐naïve persons with HIV starting integrase inhibitors compared to non‐nucleoside reversetranscriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada. J Int AIDS Soc [Internet]. 2020 Apr 15;23(4). Available 02/jia2.254845.Savinelli S, De Francesco D, Feeney E, Babalis D, Bagkeris E, Post F, et al. Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort:an observational cross‐sectional analysis. HIV Med [Internet]. 2020 Aug 20;21(7):441–52. Available from: v.128576.HIV Glasgow – Virtual, 5–8 October 2020. J Int AIDS Soc [Internet]. 2020 Oct 5;23(S7). Available from: 56167.Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. ClinInfect Dis [Internet]. 2020 Sep 12;71(6):1379–89. Available from: 67288.Harris P. Highlights of AIDS 2020. Lancet HIV [Internet]. 2020 Aug;7(8):e532. Available from: 3018203020839.Nel J, Dlamini S, Meintjes G, Burton R, Black JM, Davies NECG, et al. Southern African HIV Clinicians Society guidelines for antiretroviral therapy in adults: 2020 update. South Afr J HIV Med[Internet]. 2020 Sep 16;21(1). Available from: le/view/111510.Fuster JJ, Ouchi N, Gokce N, Walsh K. Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease. Circ Res [Internet]. 2016 May27;118(11):1786–807. Available from: .115.30688511.Guaraldi G, Draisci S, Milic J, Carli F, Besutti G, Bassoli C, et al. Fat Distribution and Density in People Living With HIV With 5% Weight Gain. HIV Glasgow 2020, Abstract O111. Available ia2.2561612.Griesel R, Maartens G, Chirehwa M, Sokhela S, Akpomiemie G, Moorhouse M, et al. CYP2B6 Genotype and Weight Gain Differences Between Dolutegravir and Efavirenz. Clin Infect Dis[Internet]. 2020 Sep 22; Available from: 0.1093/cid/ciaa1073/590999213.Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J virus Erad [Internet]. 2019 Jan 1;5(1):41–3. Available .International AIDS Society. 2020 Conference on Retroviruses and Opportunistic Infections [Internet]. 2020. Available from: ct-ebook.pdf15.Venter WDF, Sokhela S, Simmons B, Moorhouse M, Fairlie L, Mashabane N, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz,emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, n. Lancet HIV [Internet]. 2020 Oct;7(10):e666–76. Available from: 30182030241116.Calmy A, Tovar Sanchez T, Kouanfack C, Mpoudi-Etame M, Leroy S, Perrineau S, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection(NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV [Internet]. 2020 Oct;7(10):e677–87. Available S235230182030238117.Gorwood J, Bourgeois C, Pourcher V, Pourcher G, Charlotte F, Mantecon M, et al. The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and InduceInsulin Resistance in Human/Simian Adipose Tissue and Human Adipocytes. Clin Infect Dis [Internet]. 2020 Mar 13; Available from: .1093/cid/ciaa259/580425818.(WHO) WHO. Global Action Plan for the Prevention and Control of Noncommunicable Diseases. 2013.19.Adan RAH, Tiesjema B, Hillebrand JJG, Fleur SE, Kas MJH, Krom M. The MC4 receptor and control of appetite. Br J Pharmacol [Internet]. 2006 Dec;149(7):815–27. Available .Flegal KM, Kit BK, Orpana H, Graubard BI. Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories. JAMA [Internet]. 2013 Jan 2;309(1):71.Available from: http://jama.jamanetwork.com/article.aspx?doi 10.1001/jama.2012.11390521.Hawkins T. Understanding and managing the adverse effects of antiretroviral therapy. Antiviral Res [Internet]. 2010 Jan;85(1):201–9. Available S0166354209005038

Dr Bronwyn Boschbbosch@ezintsha.orgCONTACTDETAILS Dr Joana Woodsjwoods@ezintsha.org Dr Esther Bhaskarebhaskar@ezintsha.org

Pooled analysis of weight gain across 8 randomized phase III clinical trials of first-line ART initiation occurring in 2003-2015 (N 5680) Sax. Clin Infect Dis. 2020;71:1379. MULTIVARIATE ANALYSIS OF WEIGHT GAIN FOLLOWING ART INITIATION IN RCTS Pooled analysis of weight gain

Related Documents:

INSTI: Significant weight gain. Greater magnitude of weight gain in people of African descent and women: Probably greater with DTG and BIC than RAL.4,5,6 NRTIs: Greater weight gain with TAF vs. ABC and TDF;5,6 and greater weight gain with INSTI in conjunction with TAF.1 NNRTI less conducive to weight gain.5,6,7,8

to TGA, DSC and DTG tests and the following results were drawn. Fig. 2 (a) DSC, DTG and TGA curves for pure epoxy specimen The DSC, DTG and TGA curves of pure epoxy are shown in Figure 2 (a). For pure Epoxy, the glass transition temperature is 140.4 C. The specimen is getting decomposed in

Pass print technology that have made DTG Digital an industry leader. The M2 series machine is designed with a bespoke firmware specifically created for optimal print quality at higher production speeds by adoption of greater ink droplet control and accurate placement on the garment.

Stat 152 - Weight Gain December 15, 2006 Figure 6: Weight gain vs. courses taken tween workload and weight gain. While it can be ar-gued that students under high stress eat less healthy meals, and may gain weight as a result, they also more likely to eat irregularly. Figures 5 and 6 which shows how weight gain is related to unit load and

Embroidery and DTG Marketing Guide Page 1 of 8 Starting your business off with both an Embroidery Machine and a Summit DTG Direct to Garment printer is one of the best decisions you will make. It gives you the opportunity to go after any market or niche

marked weight gain group the mean weight gain was 11.4 kg 4.9 kg (range 5.5-30.1 kg). The mean overall weight change in the 70 patients was 6.9 kg 5.8 kg (range —4.0-30.1 kg). The highest maximum weight gain observed was 54% of initial body weight for VPA. This corresponded to a 30 kg weight gain over a period of 15 months.

weight gain compared to ABC, TDF and ZDV 3 rd Agent: Compared to EFV, the initiation of BIC or DTG, EVG/c and RPV was associated with an increased risk of 10% weight gain. Graph: Stepwise model selection was used to identify which baseline risk factors were associated with significant \ 攀 尩 weig\൨t gain in individuals .

Machine learning (ML) and artificial intelligence (AI) have been around for many years. However, in the last 5 years, remarkable progress has been made using multilayered neural networks in diverse areas such as image recognition, speech recognition, and machine translation. AI is a general purpose technology that is likely to impact many industries. In this chapter I consider how machine .