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Title
Risks of hypertension with first-line dolutegravir (DTG) and tenofovir alafenamide (TAF) in the NAMSAL and ADVANCE trials
Presenter
Francois Venter
Authors
F. Venter1, S. Sokhela1, B. Bosch1, G. Akpomiemie1, M. Mirchandani2, K. McCann2, M. Mpoudi-Etame3, T. Tovar Sanchez4, M.-a.-Q. Bousmah5,6, A. Calmy7, E. Delaporte4,8, C. Kouanfack9,10,11,12, A. Hill13
Institutions
1Ezintsha, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa, 2Imperial College London, Faculty of Medicine, London, United Kingdom, 3Military Hospital Region N°1, Yaoundé, Cameroon, 4University of Montpellier, TransVIHMI, Montpellier, France, 5SESSTIM: University of Aix Marseille, Inserm, Marseille, France, 6Université Paris Cité, Inserm, Ceped, Paris, France, 7Genva University Hospitals, Division of Infectious Diseases, HIV-AIDS Unit, Geneva, Switzerland, 8Montpellier University Hospital Center, Montpellier, France, 9University of Dschang, Faculty of Medicine and Pharmaceutical Sciences, Dschang, Cameroon, 10Yaoundé Central Hospital, Yaoundé, Cameroon, 11Yaoundé Central Hospital, Cameroon ANRS-site, Yaoundé, Cameroon, 12CREMER, Yaoundé, Cameroon, 13University of Liverpool, Department of Pharmacology and Therapeutics, Liverpool, United Kingdom

BACKGROUND: Hypertension is a leading cause of death in sub-Saharan Africa, with a high background prevalence in the general population. First-line use of TAF and DTG lead to higher risks of clinical obesity than tenofovir disoproxil fumarate (TDF) or efavirenz (EFV). Clinical obesity increases the risks of hypertension and other non-communicable diseases (NCDs).
METHODS: In the NAMSAL trial, 613 PLWH in Cameroon were randomised to TDF/3TC/DTG or TDF/3TC/EFV (EFV low-dose). In the ADVANCE trial, 1053 PLWH in South Africa were randomised to TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV. In both trials, blood pressure was measured at every study visit. Grade 1 hypertension was defined as SBP/DBP >140/90 mmHg. In ADVANCE, all participants developing Grade 1 hypertension were given antihypertensives. In NAMSAL, <1% of participants were given anti-hypertensives, as funding was not available.
RESULTS: In NAMSAL <1% of participants were treated with anti-hypertensive drugs. By Week 192, 31% of participants developed Grade 1 hypertension on TDF/FTC/DTG, versus 19% on TDF/3TC/EFV (p=0.002). In multivariate analysis, Grade 1 hypertension was significantly correlated with use of DTG, age, sex and BMI (p<0.01 for each comparison). In ADVANCE, 6% of participants were already being treated for hypertension at baseline, rising to 20% by Week 192. Treatment-emergent Grade 1 hypertension was diagnosed for 42/315 (13%) participants on TAF/FTC/DTG, 33/316 (10%) on TDF/FTC/DTG, and 25/314 (8%) taking TDF/FTC/EFV. The risk of Grade 1 hypertension was significantly higher for TAF/FTC/DTG versus TDF/FTC/EFV (p=0.04). However, 94% of participants developing hypertension were given anti-hypertensives. By Week 192, there was no significant difference in mean SBP or Grade 1 hypertension between the arms.
CONCLUSIONS: In the NAMSAL and ADVANCE trials, first-line use of DTG was associated with significantly higher risks of treatment-emergent hypertension, especially when combined with TAF. In NAMSAL, where hypertension was not consistently treated, risks of hypertension remained higher for TDF/3TC/DTG through Week 192. However in ADVANCE, most cases of hypertension were successfully treated, and there was no significant difference between treatment arms by Week 192. Hypertension can be diagnosed and treated with low-cost generic drugs. Mass HIV treatment programmes need to include support and funding for diagnosis and treatment for hypertension and other NCDs.