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HIV-1-infectionPhase 3IMPALANCT05546242

Improving HIV-1 Control in Africa With Long Acting Antiretrovirals

A Phase 3 study testing Cabotegravir/Rilpivirine and Antiretroviral in people with HIV-1-infection, run by MRC/UVRI and LSHTM Uganda Research Unit at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

IMPALA is a randomized, open-label, multicenter, interventional study of 540 virologically suppressed HIV-1 infected adults who have a history of sub-optimal adherence to daily oral ART and/or engagement in HIV care. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1-infection
What is being tested?
Cabotegravir/Rilpivirine and Antiretroviral
Could I receive a placebo?
No, everyone receives an active treatment
How many people
540 participants
Where
7 sitesin 3 countries
Study dates
8 Dec 2022to 20 Mar 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age and above
  • HIV-1 infection confirmed in clinic records or by study team.
  • Two consecutive HIV-1 VL <200 copies/mL ≥3 months apart prior to randomization.
  • On an oral regimen of 2NRTI + DTG as part of first line ART
  • Is identified as a participant with a history of, sub-optimal ART adherence or engagement in care based on one or more of the following criteria:
  • Documented detectable HIV-1 VL (>1000 c/mL) on all-oral ART (EFV/NVP or DTG-based) in the prior 2 years despite being ART-experienced for
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  • ≥3 months.
  • History of being lost to follow-up from care (>4 weeks elapsed since a missed scheduled clinic appointment or refill in the prior 2 years).
  • Failed to link to HIV care despite ≥3 months elapsed since HIV diagnosis.
  • Females: human chorionic gonadotrophin (HCG) negative and willing to use one highly effective form of contraception if woman of reproductive potential
  • Must sign informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
  • Willing and able to attend all clinic appointments.

Who cannot join

  • Not virologically suppressed (VL<200 c/mL) for ≥3 months at the end of the screening process.
  • Previous use, or intention to use, protease inhibitor-based ART at any time.
  • Evidence of prior HIV-1 resistance test with NNRTI drug resistance mutations (other than K103N) and/or INSTI drug resistance mutations.
  • Unwillingness to receive 2 injections on a 2 monthly basis.
  • Unwilling to use a form of contraception.
  • Pregnant, breastfeeding or planning to become pregnant during the study period.
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  • Requires tuberculosis therapy or other drug with clinically relevant drug interaction
  • High risk of seizures, including participants with an unstable or poorly controlled seizure disorder.
  • Has active TB or other mycobacterial disease and requires treatment.
  • Advanced liver disease, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or history of cirrhosis.
  • Chronic Hepatitis C with planned or anticipated use of Hep C therapy
  • Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb) as follows:
  • Participants positive for HBsAg are excluded
  • Participants negative for HBsAg but positive for HBcAb, with no evidence of HBsAb are excluded NOTE: Participants positive for HBcAb due to prior infection (negative HBsAg status) and with evidence of HBsAb have some immunity to HBV and have low risk of reactivation so are not excluded.
  • Current or anticipated need for chronic anticoagulation therapy.
  • Previous use of oral or injectable CAB or RPV.
  • Any Grade 4 laboratory abnormality at the conclusion of screening process.
  • Creatinine clearance (CrCl) <50 mL/min/1.732 by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation.
  • Alanine aminotransferase (ALT) > 3×upper limit of normal (ULN).
  • Has a tattoo or other dermatological condition overlying the gluteus region that may interfere with interpretation of ISRs.
  • Has ongoing or clinically significant medical conditions that in the opinion of the investigator may interfere with the absorption, distribution, metabolism or excretion of the study interventions or could affect participant safety.
  • Has pre-existing physical or mental condition which, in the opinion of the investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
  • Known allergies, hypersensitivity, or intolerance to cabotegravir or rilpivirine or its excipients.
  • Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study intervention or is currently enrolled in another interventional study.
  • Has received any prohibited medication listed in Section 6.8.2, Prohibited Medications and Non-drug Therapies and is unwilling or unable to switch to an alternate medication.
  • Has been treated with any of the following agents within 28 days of Screening:
  • Radiation therapy.
  • Cytotoxic chemotherapeutic agents.
  • Tuberculosis therapy with the exception of isoniazid (isonicotinyl hydrazid, INH).
  • Anticoagulation agents (e.g., warfarin and direct oral anticoagulants).
  • Is using immunomodulators that alter immune responses (such as chronic systemic corticosteroids, interleukins, or interferons). Note: Participants using short-term steroid tapers, topical, inhaled and intranasal corticosteroids, topical imiquimod are eligible for enrolment.
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
  • QTc interval >450 ms (if QTc interval is >450 ms on the ECG read out, then it should be corrected according to Fridericia; https://www.mdcalc.com/corrected-qt-interval-qtc) within 90 days prior to study entry.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Uganda3 sites

  • Entebbe Grade A Hospital

    Entebbe

  • JCRC Fort Portal

    Fort Portal

  • Infectious Diseases Institute

    Kampala

Other trials in Uganda

Kenya2 sites

  • Jaramogi Oginga Odinga Teaching & Referral Hospital

    Kisumu

  • Kenyatta National Hospital

    Nairobi

Other trials in Kenya

South Africa2 sites

  • Desmond Tutu Health Foundation

    Cape Town

  • CAPRISA

    Durban

Other trials in South Africa

About this study

Official title: A Phase 3b Randomised, Multicentre, Open-label Study Evaluating the Effectiveness of Switching to Two-monthly Long-acting Injectable Cabotegravir and Rilpivirine From First-line Oral Antiretroviral Therapy in HIV-1 Positive Virologically Suppressed Adults With a History of, or at Risk of, Sub-optimal HIV Control in Sub-Saharan Africa

IMPALA is a randomized, open-label, multicenter, interventional study of 540 virologically suppressed HIV-1 infected adults who have a history of sub-optimal adherence to daily oral ART and/or engagement in HIV care. The study will seek to demonstrate non-inferior antiviral effectiveness of the 2-monthly long-acting injectable combination of cabotegravir/rilpivirine as compared to continuation of first line oral antiretroviral therapy.

Read the detailed description

IMPALA is a randomized, open-label, multicenter, interventional study of 540 virologically suppressed (<200 c/mL) HIV-1 infected adults (18 years or older) who have a history of sub-optimal adherence to daily oral ART and/or engagement in HIV care. IMPALA seeks to demonstrate the non-inferior antiviral effectiveness of switching to long acting injectable rilpivirine (RPV LA) plus long acting injectable cabotegravir (CAB LA) given every 2 months (Q2M CAB LA + RPV LA) by IM compared to the continuation of first-line daily oral ART containing 2 nucleoside reverse transcriptase inhibitor (NRTIs) plus an integrase strand transfer inhibitor (INSTI; dolutegravir [DTG]).

After providing written informed consent, participants will be evaluated for eligibility during the screening period. Participants who are viremic (HIV VL >200 c/mL) at the time of screening will be virologically suppressed (for >3 months) on a regimen of 2 NRTIs plus DTG prior to randomization. On Day 1 virologically suppressed (<200 c/mL for at least 3 months) individuals will be randomized 1:1 to either continue daily oral ART (2 NRTI + DTG, control arm), or switch to Q2M CAB LA + RPV LA IM, the intervention arm. Those randomized to the intervention arm will be offered either optional oral lead-in (OLI) of 1 month daily oral CAB and RPV or a direct to injection (DTI) approach. This decision to dose with or without an OLI Phase will be determined by the study participant following the informed consent discussion with the investigator. The total duration of the study will be 24 months. Any participant who has received at least a single dose of CAB LA + RPV LA and discontinues the regimen for any reason before Month 24 must start suppressive daily oral ART within 2 months of the last injection. There will be an optional real-world extension phase, provided the regimen is deemed to be non-inferior at Month 12 and 24.

Conditions
HIV-1-infection
Being tested
Cabotegravir/Rilpivirine, Antiretroviral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabotegravir/RilpivirineDrug

    Also called Vocabria/Rekambys

    injectable long-acting cabotegravir 600mg + long-acting rilpivirine 900mg administered every 2 months

  • AntiretroviralDrug

    Also called 2NRTIs + dolutegravir 50mg once daily

    Oral antiretroviral therapy in the form of 2NRTIs + dolutegravir 50mg administered daily

Study groups in NCT05546242
Study groupRoleWhat they receive
CAB LA + RPV LA ArmExperimentalThe first 4 weeks of the treatment differ depending on whether participant opts for direct to injection (DTI) or Oral lead-in (OLI). DTI: participants will remain on daily oral ART for 4weeks after randomization and will receive the 1st injection of IM CAB LA 600mg+RPV LA 900mg at the Month 1 visit. 2nd injections administered at Month 2, followed by maintenance injections every 2 months (Q2M) OLI: participants will receive the study intervention in 2 phases: 1. Participants will receive CAB 30mg+RPV 25mg OD for 4weeks to be taken daily with food. The purpose of the optional OLI Phase is to allow an opportunity for participants to assess tolerability of the combination prior to administration of the injectables. There is no proven benefit to this approach 2. After 4weeks participants return for the Month 1 visit to receive the 1st IM CAB LA 600mg+RPV LA 900mg injections. The 2nd injections administered at Month 2 and then continuation injections will be administered Q2M
Receives: Drug: Cabotegravir/Rilpivirine
ART GroupActive comparatorParticipants will take a daily oral combination of 2 NRTIs plus DTG 50mg. Ideally, the single tablet fixed-dose combination regimen of (tenofovir disoproxil fumarate [TDF] 300 mg + lamivudine [3TC] 300 mg (or emtricitabine [FTC] 200 mg) + DTG 50 mg) will be used as per local country guidelines up to Month 24. If there are preexisting reasons why TDF or 3TC cannot be used as the NRTI backbone then alternative NRTIs are acceptable. Participants will be permitted to switch daily oral ART drugs in case of toxicity, after discussion with the coordinating center.
Receives: Drug: Antiretroviral

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HIV-1 viral load at 12 months

    Proportion with plasma HIV-1 viral load (VL) <50 c/mL at 12 months (by Food and Drug Administration [FDA] snapshot algorithm)

    Measured: 12 months

Secondary outcomes (16)

  1. Confirmed virologic failure on 2 consecutive occasions

    Proportion with confirmed virologic failure (CVF) [plasma HIV-1 VL ≥200 c/mL on 2 consecutive occasions]

    Measured: 12 months

  2. Confirmed virologic failure on 2 consecutive occasions

    Proportion with confirmed virologic failure (CVF) [plasma HIV-1 VL ≥200 c/mL on 2 consecutive occasions]

    Measured: 24 months

  3. Lost to follow up

    Proportion with LTFU [>4 weeks elapsed since their last missed appointment]

    Measured: 12 months

  4. Lost to follow up

    Proportion with LTFU [>4 weeks elapsed since their last missed appointment]

    Measured: 24 months

  5. HIV-1 viral load <200c/mL

    Proportion with plasma HIV-1 VL <200 c/mL

    Measured: 12 months

  6. Virologic response

    Proportion with plasma HIV-1 VL <50 c/mL

    Measured: 12 months and 24 months

  7. Virologic non-response

    Proportion with plasma HIV-1 VL >=50 c/mL (by FDA snapshot algorithm)

    Measured: 24 months

  8. Change in CD4+ T cell count

    Change in CD4+ T cell count from baseline

    Measured: 12 months

  9. Change in CD4+ T cell count

    Change in CD4+ T cell count from baseline

    Measured: 24 months

  10. HIV disease progression

    Incidence of HIV disease progression (HIV/AIDS related hospitalizations, illness or deaths)

    Measured: 24 months

  11. Adverse Events

    Incidence of adverse events (AEs)

    Measured: 12 months

  12. Adverse Events

    Incidence of adverse events (AEs)

    Measured: 24 months

  13. Grade 3 and 4 Adverse Events

    Incidence of AEs, Grade 3 and 4 excluding injection site reactions

    Measured: 12 months

  14. Grade 3 and 4 Adverse Events

    Incidence of AEs, Grade 3 and 4 excluding injection site reactions

    Measured: 24 months

  15. Injection Site Reactions

    Frequency of injection site reactions of any grade

    Measured: 24 months

  16. Resistance Emergence

    Frequency of emergence of new integrase strand transfer inhibitor and non-nucleoside reverse transcriptase inhibitor resistance mutations in those who develop virologic failure

    Measured: 12 months and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2022
  2. Study start8 Dec 2022
  3. Primary completion14 Apr 2025
  4. Study completion20 Mar 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
parallel open-label phase 3b study. Participants will be randomised to continuing current therapy or switching to injectable therapy.
Masking
None (open label)
Enrolment
540 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05546242
Sponsor's protocol ID
TMC278LAHTX3005
Acronym
IMPALA
Status last verified
Oct 2026
First submitted
16 Sep 2022
Last updated
9 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cresswell FV, Kitonsa J, Norcross C, Tumusiime V, Ombajo LA, Garrett N, Kassim S, Owarwo NC, Laker Odongpiny EA, Yawe I, Mahomed S, Mugerwa H, Kafeero PL, Nkuranga J, Bahemuka U, Nabbuto J, Ankunda V, Nabaggala P, Ogwang C, Kimbugwe G, Kakande A, Singh U, van der Vendt D, Onyango A, Koile E, Lawrence DS, Idahosa A, van Eygen V, Addo Boateng F, Eshun-Wilsonova I, Grint DJ, Ruzagira E; IMPALA Study Group. Long-Acting HIV Therapy in African Adults with Adherence Challenges. N Engl J Med. 2026 Oct 15;395(15):1505-1518. doi: 10.1056/NEJMoa2518753.

    PubMed 42874104

  • Tumusiime VB, Ruzagira E, Norcross C, Eshun-Wilsonova I, Kitonsa J, Bahemuka UM, Grint D, Kimbugwe G, Kakande A, Lawrence DS, Mwendia F, Van Solingen R, Van Eygen V, Addo Boateng F, Cresswell F; IMPALA study team. 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). Wellcome Open Res. 2025 Mar 28;10:166. doi: 10.12688/wellcomeopenres.23363.1. eCollection 2025.

    PubMed 41040645

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cabotegravir/Rilpivirine and Antiretroviral in people with HIV-1-infection, run by MRC/UVRI and LSHTM Uganda Research Unit at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Uganda, Kenya, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HIV-1 viral load at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05546242, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.

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