. 2025 Mar 28:10:166.

doi: 10.12688/wellcomeopenres.23363.1. eCollection 2025.

Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA)

Victoria Babirye Tumusiime¹, Eugene Ruzagira^{1

2}, Claire Norcross^{1

3}, Ingrid Eshun-Wilsonova⁴, Jonathan Kitonsa^{1

3}, Ubaldo Mushabe Bahemuka¹, Daniel Grint², Geofrey Kimbugwe¹, Ayoub Kakande¹, David S Lawrence^{5

6

7}, Fridah Mwendia⁸, Rodica Van Solingen⁹, Veerle Van Eygen⁹, Fafa Addo Boateng¹⁰, Fiona Cresswell^{1

3

5}; IMPALA study team

Collaborators, Affiliations

Collaborators

IMPALA study team:
Idahosa Awonukhe, Noami Waita, Willemijn Rein VanDerHorst, Derrick Addy, Emilija Tomic, Noela Clara Owarwo, Eva Laker, Sylivia Cornelia Nassiwa, Ibrahim Yawe, Adolf Alinaitwe, Henry Mugerwa, Loice Achieng Ombajo, Joseph Nkuranga, Nigel Garrett, Sharana Mahomed, Bongi Zuma, Nirosha Gokul, Sheetal Kassim, Dorothie VanderVendt, Fatim Abrahams, Ruanne Barnabas, Jessie Heitner, Agnes Ssali, Dominic Bukenya, Violet Ankunda, Ayub Kakande, Charles Ogwang, Priscilla Balungi, Jane Nabbuto, Florence Nambaziira, Charliene Katurole, Jascent Nassuna, Diana Gibb, Cissy Kityo, Chloe Orkin, Simiso M Sokhela, Ivy Kaunda, Geofrey Kimbugwe, Paddy Kafeero, Phiona Nabaggala, Mina Ssali Nakawuka, Joseph Lutaakome, Gloria Lubega, Moses Kibirige, Gertrude Nabulime, Margaret Nalaaki, Peace Bukirwa, Deus Wangi, Dorothy Abigaba, Antonio Ssewakambo, Daniel Opoka, Slyvia Namaganda, Henry Rogers Isiko, Max Okwero, Annet Nankya, Diana Namuddu, Hamza Mayanja, Patricia Nerima, Jesca Asienzo, Doerieyah Reynolds, Agatha Theuri, Elizabeth Kamau, Felix Humwa, Jacqueline Nyange, Simon Wahome, Eve Koile, Susan Wanjiru Maina, Susan Onywera, Victor Omodi, Edwin Othieno, Arnold Onyango, Gerald Kiambi, Martha Atandi, Beryl Handa, Amos Ingubo, Fahkri Williams, Yashna Singh, Melanie Maclachlan, Zareen Dhansay, Sherisce Govender, Sumaiyya Moosa, Viwe Soko, Awethu Fuzie, Rochel Jacobs, Mary Sihlangu, Yamkela Sapepa, Monica Vogt, Upasna Singh, Nicola Bodley, Lorna Dias, Carol Minnie, Mpume Khoza, Renita David, Lungile Maziya, Silindile Molefe, Nokuphiwa Zondi, Amanda Khuzwayo, Nivashnne Naicker, Atika Moosa, Nomfundo Mbatha

Affiliations

¹ HIV interventions, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Central Region, 256, Uganda.
² Department of Infectious Diseases Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK.
³ Global Health and Infectious, Brighton and Sussex Medical School, Brighton, England, UK.
⁴ Johnson & Johnson, CapeTown, South Africa.
⁵ Department of Clinical Research, London School of Hygiene and Tropical Medicine Faculty of Infectious and Tropical Diseases, London, England, UK.
⁶ Botswana Harvard Health Partnership, Gaborone, Botswana.
⁷ School of Pathology, Faculty of Health Sciences , University of Witwatersrand, Johannesburg, South Africa.
⁸ Johnson & Johnson, East Africa, Nairobi, Kenya.
⁹ Jansenn Research and Development, Beerse, Belgium.
¹⁰ Johnson & Johnson Middle East FZ LLC, Accra, Ghana.

PMID: 41040645
PMCID: PMC12485332
DOI: 10.12688/wellcomeopenres.23363.1

Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA)

Victoria Babirye Tumusiime et al. Wellcome Open Res. 2025.

. 2025 Mar 28:10:166.

doi: 10.12688/wellcomeopenres.23363.1. eCollection 2025.

Authors

Collaborators

IMPALA study team:
Idahosa Awonukhe, Noami Waita, Willemijn Rein VanDerHorst, Derrick Addy, Emilija Tomic, Noela Clara Owarwo, Eva Laker, Sylivia Cornelia Nassiwa, Ibrahim Yawe, Adolf Alinaitwe, Henry Mugerwa, Loice Achieng Ombajo, Joseph Nkuranga, Nigel Garrett, Sharana Mahomed, Bongi Zuma, Nirosha Gokul, Sheetal Kassim, Dorothie VanderVendt, Fatim Abrahams, Ruanne Barnabas, Jessie Heitner, Agnes Ssali, Dominic Bukenya, Violet Ankunda, Ayub Kakande, Charles Ogwang, Priscilla Balungi, Jane Nabbuto, Florence Nambaziira, Charliene Katurole, Jascent Nassuna, Diana Gibb, Cissy Kityo, Chloe Orkin, Simiso M Sokhela, Ivy Kaunda, Geofrey Kimbugwe, Paddy Kafeero, Phiona Nabaggala, Mina Ssali Nakawuka, Joseph Lutaakome, Gloria Lubega, Moses Kibirige, Gertrude Nabulime, Margaret Nalaaki, Peace Bukirwa, Deus Wangi, Dorothy Abigaba, Antonio Ssewakambo, Daniel Opoka, Slyvia Namaganda, Henry Rogers Isiko, Max Okwero, Annet Nankya, Diana Namuddu, Hamza Mayanja, Patricia Nerima, Jesca Asienzo, Doerieyah Reynolds, Agatha Theuri, Elizabeth Kamau, Felix Humwa, Jacqueline Nyange, Simon Wahome, Eve Koile, Susan Wanjiru Maina, Susan Onywera, Victor Omodi, Edwin Othieno, Arnold Onyango, Gerald Kiambi, Martha Atandi, Beryl Handa, Amos Ingubo, Fahkri Williams, Yashna Singh, Melanie Maclachlan, Zareen Dhansay, Sherisce Govender, Sumaiyya Moosa, Viwe Soko, Awethu Fuzie, Rochel Jacobs, Mary Sihlangu, Yamkela Sapepa, Monica Vogt, Upasna Singh, Nicola Bodley, Lorna Dias, Carol Minnie, Mpume Khoza, Renita David, Lungile Maziya, Silindile Molefe, Nokuphiwa Zondi, Amanda Khuzwayo, Nivashnne Naicker, Atika Moosa, Nomfundo Mbatha

Affiliations

¹ HIV interventions, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Central Region, 256, Uganda.
² Department of Infectious Diseases Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK.
³ Global Health and Infectious, Brighton and Sussex Medical School, Brighton, England, UK.
⁴ Johnson & Johnson, CapeTown, South Africa.
⁵ Department of Clinical Research, London School of Hygiene and Tropical Medicine Faculty of Infectious and Tropical Diseases, London, England, UK.
⁶ Botswana Harvard Health Partnership, Gaborone, Botswana.
⁷ School of Pathology, Faculty of Health Sciences , University of Witwatersrand, Johannesburg, South Africa.
⁸ Johnson & Johnson, East Africa, Nairobi, Kenya.
⁹ Jansenn Research and Development, Beerse, Belgium.
¹⁰ Johnson & Johnson Middle East FZ LLC, Accra, Ghana.

PMID: 41040645
PMCID: PMC12485332
DOI: 10.12688/wellcomeopenres.23363.1

Abstract

Long-acting (LA) injectable therapy as treatment for HIV-1 infection offers reduced dosing frequency, increased discretion and provides an alternative to two or three-drug daily oral combinations. A parenteral LA formulation of cabotegravir (CAB) and rilpivirine (RPV) given by intramuscular (IM) injection every 2 months (CAB LA + RPV LA Q2M) has shown safety and efficacy in phase 3/3b trials and could increase treatment satisfaction and improve adherence in sub-Saharan Africa. IMPALA (IMProving HIV-1 Control in Africa using Long-Acting Antiretrovirals) is a randomized, controlled, open-label, multicentre, interventional study in Uganda, Kenya, and South Africa of 540 virologically suppressed adults living with HIV-1 infection with a history of sub-optimal adherence to daily oral ART . IMPALA seeks to demonstrate the non-inferior antiviral effectiveness of switching to CAB LA + RPV LA Q2M, compared to the continuation of first-line daily oral ART containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus dolutegravir (DTG). After providing informed consent, participants are screened for eligibility. Those who are viraemic (HIV RNA ≥200 copies/mL) at screening will be suppressed (<200 copies/mL for ≥3 months) on oral ART prior to randomization. On Day 1, individuals will be randomized 1:1 to either continue daily oral ART, or switch to CAB LA + RPV LA Q2M, (intervention arm) with or without a 1-month oral lead consisting of once daily oral CAB + RPV. The total follow-up period is 24 months. The primary endpoint is HIV-1 RNA <50 copies/ml at 12 months by FDA snapshot. Initial: TMC278LAHTX3005 Version Amendment 1, 30 September 2022 Superseded by: TMC278LAHTX3005 Version Amendment 2, 3 June 2024 This clinical trial was registered on Clinical Trials.gov on 19 September 2022 (NCT05546242), available from https://clinicaltrials.gov/ct2/show/NCT05546242. The study was also registered on Pan African Clinical Trials Registry on 23 January 2023 (PACT202301600757432TMC278LAHTX3005), available from https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24291.

Keywords: Antiretroviral therapy; Cabotegravir; HIV-1; Long-acting; Rilpivirine; Treatment adherence.

Plain language summary

The IMPALA study is an open-label phase 3b randomized clinical trial in Uganda, Kenya, and South Africa. It includes 540 adults with HIV-1 who have previously struggled to take daily HIV pills and have had high levels of HIV virus in their blood. Study participants have the virus suppressed with HIV pills and are then assigned, by chance, to either continue their daily oral HIV pills or switch to the long-acting HIV treatment comprising two drugs – cabotegravir and rilpivirine – which are given as two separate intramuscular injections every two months. Participants are followed for 24 months, and the trial will measure whether the injectable treatment is just as effective and safe as the daily oral treatment. The main goal is seeing if the virus remains suppressed after 12 months and comparing these results between the oral and injectable treatment.

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Conflict of interest statement

Competing interests: The trial has been funded by Johnson & Johnson. Creswell has also received research funding to institution from Gilead, Wellcome and ViiV. Van Solingen & Van Eygen are employees of Janssen Research and Development, Beerse, Belgium and own stock in Janssen Pharmaceuticals companies of Johnsons & Johnson. Boateng is an employee of Johnson & Johnson Middle East FZ LLC, Ghana and owns Johnson & Johnson stock.

Figures

**Figure 1.. Schematic overview of the IMPALA Trial.**

See this image and copyright information in PMC

References

1. Osler M, Hilderbrand K, Goemaere E, et al. : The continuing burden of advanced HIV disease over 10 years of increasing antiretroviral therapy coverage in South Africa. Clin Infect Dis. 2018;66(suppl_2):S118–25. 10.1093/cid/cix1140 - DOI - PMC - PubMed
1. Ellis J, Bangdiwala AS, Cresswell FV, et al. : The changing epidemiology of HIV-associated adult meningitis, Uganda 2015–2017. Open Forum Infect Dis. 2019;6(10): ofz419. 10.1093/ofid/ofz419 - DOI - PMC - PubMed
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1. UNAIDS: UNAIDS fact sheet 2024. 2024; [cited 2024 Aug 26]. Reference Source
1. UNAIDS: Understanding fast-track: accelerating action to end the AIDS epidemic by 2030.UNAIDS,2015; [cited 2024 May 6]. Reference Source

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Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA)

Collaborators

Affiliations

Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA)

Authors

Collaborators

Affiliations

Abstract

Plain language summary

Conflict of interest statement

Figures

References

Associated data

LinkOut - more resources

Full Text Sources

Medical