Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens

Simiso Sokhela¹, Willem D F Venter¹, Bronwyn Bosch¹, Joana Woods¹, Kaitlyn McCann², Godspower Akpomiemie¹, Nomathemba Chandiwana¹, Nkuli Mashabane¹, Angela Tembo¹, Bryony Simmons³, Samanta Lalla-Edward¹, Mark J Siedner^{4

5}, Phumla Sinxadi^{6

7}, Lucas Hermans^{1

8}, Lee Fairlie⁹, Alinda Vos^{1

10}, Elaine Abrams¹¹, Jennifer M Manne-Goehler¹², Michelle Moorhouse¹³, Polly Clayden¹⁴, Shane Norris¹⁵, Ambar Qavi², Matthew Chersich⁸, Masebole Masenya⁸, Natasha Arulappan¹, Andrew Hill¹⁶

Affiliations

¹ Wits Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² School of Public Health, Imperial College London, London, UK.
³ LSE Health, London School of Economics and Political Science, Imperial College London, London, UK.
⁴ Africa Health Research Institute, KwaZulu-Natal, South Africa.
⁵ Harvard Medical School, Boston, Massachusetts, USA.
⁶ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁷ SAMRC/UCT Platform for Pharmacogenomics Research and Translation, South African Medical Research Council, Cape Town, South Africa.
⁸ Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁹ Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
¹¹ Mailman School of Public Health and Department of Pediatrics, Vagelos College of Physicians and Surgeons, ICAP at Columbia University, Columbia University, New York, New York, USA.
¹² Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹³ ViiV Healthcare, Johannesburg, South Africa.
¹⁴ HIV i-Base, London, UK.
¹⁵ South African Medical Research Council, Developmental Pathways for Health Research Unit, Department of Pediatrics, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Department of Translational Medicine, Liverpool University, Liverpool, UK.

PMID: 38529213
PMCID: PMC10962246
DOI: 10.1093/ofid/ofae007

Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens

Simiso Sokhela et al. Open Forum Infect Dis. 2024.

. 2024 Jan 24;11(3):ofae007.

doi: 10.1093/ofid/ofae007. eCollection 2024 Mar.

Authors

Affiliations

¹ Wits Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² School of Public Health, Imperial College London, London, UK.
³ LSE Health, London School of Economics and Political Science, Imperial College London, London, UK.
⁴ Africa Health Research Institute, KwaZulu-Natal, South Africa.
⁵ Harvard Medical School, Boston, Massachusetts, USA.
⁶ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁷ SAMRC/UCT Platform for Pharmacogenomics Research and Translation, South African Medical Research Council, Cape Town, South Africa.
⁸ Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁹ Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
¹¹ Mailman School of Public Health and Department of Pediatrics, Vagelos College of Physicians and Surgeons, ICAP at Columbia University, Columbia University, New York, New York, USA.
¹² Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹³ ViiV Healthcare, Johannesburg, South Africa.
¹⁴ HIV i-Base, London, UK.
¹⁵ South African Medical Research Council, Developmental Pathways for Health Research Unit, Department of Pediatrics, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Department of Translational Medicine, Liverpool University, Liverpool, UK.

PMID: 38529213
PMCID: PMC10962246
DOI: 10.1093/ofid/ofae007

Abstract

Background: ADVANCE compared 3 World Health Organization-recommended first-line regimens in participants with HIV who were antiretroviral naive.

Methods: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtricitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks.

Results: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm.

Conclusions: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes.

Keywords: dolutegravir; obesity; resistance; suppression; tenofovir.

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Figures

**Figure 1.**
Flowchart for randomization to each treatment group. DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

**Figure 2.**
Time to clinical obesity by treatment arm and baseline CD4 count. DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

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Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens

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Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens

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