{"id":37684,"date":"2020-04-17T07:53:45","date_gmt":"2020-04-17T07:53:45","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=37684"},"modified":"2020-09-17T21:58:43","modified_gmt":"2020-09-17T21:58:43","slug":"predicted-diabetes-risk-with-first-line-art-regimens-results-from-the-advance-trial-2","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/37684","title":{"rendered":"Predicted diabetes risk with first-line ART regimens: results from the ADVANCE trial"},"content":{"rendered":"

\"\"Polly\u00a0Clayden,\u00a0HIV\u00a0i-Base<\/b><\/p>\n

Increased risk of diabetes predicted for people receiving tenofovir alafenamide (TAF), emtricitabine (FTC) and dolutegravir (DTG) in the ADVANCE trial \u2013 according to an analysis presented at CROI 2020. [1]<\/strong><\/p>\n

In ADVANCE 1053 treatment-naive people in South Africa were randomised to one of three first-line ART regimens. More participants taking first-line TAF\/FTC\/DTG developed clinical obesity compared to tenofovir disoproxil fumarate (TDF)\/FTC\/DTG and TDF\/FTC\/efavirenz (EFV). [2]<\/p>\n

The analysis of predicted risks associated with obesity in the study set out to answer the following research questions: \u00a0<\/span><\/p>\n

    \n
  1. What changes are seen in markers of cardiovascular risk and diabetes?<\/li>\n
  2. Can we use risk equations to predict the risk of cardiovascular disease or diabetes from these changes?<\/li>\n<\/ol>\n

    At baseline characteristics were balanced across the three study arms, participants were 99% black and 59% women. The median age was 31 years, approximately 20% had viral load above 100,000 copies\/mL and CD4 was about 350 cells\/mm3<\/sup>.\u00a0 \u00a0 \u00a0<\/span><\/p>\n

    Women weighed more than men and had higher BMI: approximately 27 vs 21 kg\/m2<\/sup>. Just over half the participants had a normal BMI at baseline, and approximately a quarter were overweight.\u00a0<\/span><\/p>\n

    Mean change in weight at week 96 was greater in women than men. Mean weight increase for women in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms was 8 kg, 5 kg and 3 kg, respectively. For men, mean weight increase for the respective regimens was 5 kg, 4 kg and 1 kg.<\/p>\n

    Treatment-emergent obesity occurred in 28%, 17% and 12% of women in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms, respectively. Compared to 7%, 5% and 3% of men in the respective treatment arms.<\/p>\n

    There was less increase in cholesterol in the TDF\/FTC\/DTG arm than in the other two arms (see Table 1). Total cholesterol and LDL increased in the TAF\/FTC\/DTG arm. Fasting glucose increased more in the TDF\/FTC\/EFV arm than the other two.\u00a0<\/span><\/p>\n

    Table\u00a01:\u00a0Changes\u00a0in\u00a0laboratory\u00a0parameters\u00a0to\u00a0week\u00a096:\u00a0median\u00a0(IQR)<\/b><\/p>\n\n\n\n\n\n\n\n\n
    ART regimen\/ comparison<\/td>\n1.TAF\/FTC\/DTG (n=185)<\/td>\n2.TDF\/FTC\/DTG (n=187)<\/td>\n3.TDF\/FTC\/EFV (n=191)<\/td>\nArm 1 vs 3<\/td>\nArm 1 vs 2<\/td>\nArm 2 vs 3<\/td>\n<\/tr>\n
    Total cholesterol (mg\/dL)<\/td>\n10.4\u00a0<\/span>\n

    (-5.4 to 24)<\/p><\/td>\n

    		1.5\u00a0<\/span>\n

    (-13 to 19.7)<\/p><\/td>\n

    		13.1\u00a0<\/span>\n

    (-1.9 to 33.3)<\/p><\/td>\n

    		p=0.022<\/td>\np=0.007<\/td>\np<0.001<\/td>\n<\/tr>\n
    LDL (mg\/dL)<\/td>\n8.5\u00a0<\/span>\n

    (-6.2 to 20.5)<\/p><\/td>\n

    		2.3\u00a0<\/span>\n

    (-10.8 to 12.4)<\/p><\/td>\n

    		6.2\u00a0<\/span>\n

    (-5.0 to 22.0)<\/p><\/td>\n

    		p=0.82<\/td>\np=0.007<\/td>\np=0.013<\/td>\n<\/tr>\n
    HDL (mg\/dL)<\/td>\n4.6\u00a0<\/span>\n

    (-2.3 to 12.0)<\/p><\/td>\n

    		3.9\u00a0<\/span>\n

    (-2.3 to 12)<\/p><\/td>\n

    		9.7\u00a0<\/span>\n

    (2.3 to 19.3)<\/p><\/td>\n

    		p<0.001<\/td>\np=0.73<\/td>\np<0.001<\/td>\n<\/tr>\n
    Fasting glucose (mg\/dL)<\/td>\n19.3\u00a0<\/span>\n

    (7.7 to 34.8)<\/p><\/td>\n

    		19.3\u00a0<\/span>\n

    (0.0 to 34.8)<\/p><\/td>\n

    		27.1\n

    (11.6 to 42.5)<\/p><\/td>\n

    		p=0.0049<\/td>\np=0.21<\/td>\np<0.001<\/td>\n<\/tr>\n
    Systolic BP (mmHg)<\/td>\n3.0\u00a0<\/span>\n

    (-7.0 to 11.0)<\/p><\/td>\n

    		-1.0\u00a0<\/span>\n

    (-12.0 to 8.0)<\/p><\/td>\n

    		0.5\u00a0<\/span>\n

    (-9.0 to 8.0)<\/p><\/td>\n

    		p=0.19<\/td>\np=0.03<\/td>\np=0.35<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    Metabolic syndrome (International Diabetes Federation definition \u2013 clinical obesity plus at least two of: raised triglycerides;\u00a0reduced HDL cholesterol;\u00a0raised blood pressure; raised fasting glucose) emerged in 8%, 6% and 3% of participants in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms respectively. There were statistically significant differences between TAF\/FTC\/DTG and TDF\/FTC\/DTG at week 96 (p=0.031).\u00a0 \u00a0<\/span><\/p>\n

    The investigators used three risk equations to calculate the risk of cardiovascular events or diabetes in ADVANCE participants.<\/p>\n

    The Framingham risk equation estimates the 10-year risk of heart attack or coronary death. According to this equation, the investigators reported no significant difference and low risk across arms at baseline: 2.37%, 2.53% and 2.24% in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms respectively.<\/p>\n

    At week 96 there was a similar and\u00a0 <\/span>very modest increase in risk: +0.43%, +0.22% and +0.28 across the respective treatment arms. \u00a0 <\/span><\/p>\n

    The QRISK equation estimates the 10-year risk of developing heart attack or stroke. This equation looks at a larger number of variables than Framingham \u2013 including black African ethnicity.<\/p>\n

    According to QRISK, the baseline 10-year risk of heart attack or stroke was very low: 0.6%, 0.6% and 0.5% in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms respectively.<\/p>\n

    At week 96 there was a slightly lower borderline significant risk with TDF\/FTC\/EFV compared with TAF\/FTC\/DTG (p=0.027) \u00a0<\/span><\/p>\n

    The QDiabetes\u00a0score estimates the 10-year risk of developing diabetes. Black African ethnicity is also included among the variables in this equation.<\/p>\n

    The baseline 10 year risk score of developing diabetes was: 0.30%, 0.40% and 0.30% in the TAF\/FTC\/DTG, TDF\/FTC\/DTG and TDF\/FTC\/EFV arms respectively.<\/p>\n

    At week 96, this increased to 0.90%, 0.50% and 0.70% in the respective arms. Compared with TDF\/FTC\/DTG, the risk of diabetes was significantly higher with TAF\/FTC\/DTG (p=0.004) and with TDF\/FTC\/EFV (p=0.005). There were no significant differences between TAF\/FTC\/DTG and TDF\/FTC\/EFV.<\/p>\n

    The investigators noted that among women treated with TAF\/FTC\/DTG, weight is continuing to increase, with no sign of a plateau. The predictive models do not account for additional weight gain after week 96.<\/p>\n

    comment<\/b><\/p>\n

    There is very little additional risk of MI in this young population, but there is a significant increase in the predicted risk of diabetes for people taking TAF\/FTC\/DTG vs TDF\/FTC\/DTG.\u00a0\u00a0<\/span><\/b><\/p>\n

    For every 1000 people treated, these results suggest that an additional 4 people taking TAF\/FTC\/DTG would develop diabetes.\u00a0 The investigators have checked these results using another predictive equation (Cambridge algorithm) and seen the same.<\/b><\/p>\n

    In South Africa, with its vast HIV epidemic, this would translate into large numbers of additional diabetes cases.\u00a0\u00a0<\/b><\/p>\n

    WHO 2019 guidelines recommend TDF\/FTC\/DTG as first-line treatment. TAF\/FTC\/DTG is reserved only for special circumstances: people with osteoporosis or impaired renal function.\u00a0 The results from this analysis support the current WHO guidelines.<\/b><\/p>\n

    References<\/p>\n

      \n
    1. Hill A et al. Risks of metabolic syndrome, diabetes, and cardiovascular disease in ADVANCE trial. CROI 2020. Boston, MA. 8\u201311 March 2020. Oral abstract 81.
      \nhttps:\/\/www.croiconference.org\/abstract\/risks-of-metabolic-syndrome-diabetes-and-cardiovascular-disease-in-advance-trial<\/a><\/li>\n
    2. Clayden P. Weight gain and metabolic syndrome with dolutegravir and TAF: results from the ADVANCE trial. HTB. 15 November 2019.
      \n      https:\/\/i-base.info\/htb\/36879<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

      Polly\u00a0Clayden,\u00a0HIV\u00a0i-Base Increased risk of diabetes predicted for people receiving tenofovir alafenamide (TAF), emtricitabine (FTC) and dolutegravir (DTG) in the ADVANCE trial \u2013 according to an analysis presented at CROI 2020. [1] In ADVANCE 1053 treatment-naive people in South Africa were …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,8],"tags":[277],"class_list":["post-37684","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-side-effects","tag-croi-2020"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/37684","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=37684"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/37684\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=37684"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=37684"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=37684"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}