What side effects are associated with this type of intervention?

Common treatments for HIV, including Nucleoside Reverse Transcriptase Inhibitors (NRTIs) like Islatravir, often cause side effects such as nausea, headache, and fatigue, with more severe risks including lactic acidosis and liver toxicity. Capsid Inhibitors like Lenacapavir, being newer, have less well-documented side effects but may include gastrointestinal issues and changes in liver enzyme levels. Other common HIV treatments can also lead to side effects such as dizziness, insomnia, and potential kidney or bone density issues.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of HIV, including Nucleoside Reverse Transcriptase Inhibitors (NRTIs) like tenofovir and lamivudine, which work by inhibiting the reverse transcriptase enzyme crucial for viral replication. Capsid Inhibitors, a newer class of antiretrovirals, target the HIV capsid protein to disrupt viral assembly and disassembly processes. While Islatravir and Lenacapavir are still under study, their mechanisms are similar to these approved treatments, aiming to provide more effective and potentially less frequent dosing options for people living with HIV.

What other types of research exist?

Promising novel alternatives for HIV treatment in 2024 include long-acting injectable antiretrovirals like Cabotegravir (an integrase inhibitor) and Rilpivirine (a non-nucleoside reverse transcriptase inhibitor), which are administered monthly or bimonthly. Additionally, broadly neutralizing antibodies (bNAbs) such as VRC01 and 3BNC117 are being explored for their potential to provide long-term viral suppression and possibly contribute to an HIV cure strategy.

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Nucleoside Reverse Transcriptase Inhibitor

Islatravir + Lenacapavir for HIV

Q: What is the mechanism of action of this treatment?

Nucleoside Reverse Transcriptase Translocation Inhibitors (NRTTIs) like Islatravir work by integrating into the viral DNA during replication, causing premature chain termination and halting viral multiplication. Capsid Inhibitors such as Lenacapavir disrupt the HIV capsid, which is vital for protecting the viral RNA and enzymes necessary for replication. These mechanisms are crucial for HIV patients as they effectively suppress the virus, reduce viral load, and prevent disease progression, thereby improving quality of life and reducing the risk of transmission.

Phase 2

Waitlist Available

Research Sponsored by Gilead Sciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 24 weeks before and at screening

Be older than 18 years old

Must not have

Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN)

Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 up to week 36

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the effectiveness of taking two medications, islatravir and lenacapavir, regularly for people with HIV who already have very low virus levels. The goal is to see if this combination keeps the virus under control over several months.

Who is the study for?

This trial is for people with HIV who have maintained a viral load of less than 50 copies/mL and have been on B/F/TAF treatment for at least 24 weeks. They shouldn't have had previous virologic failures, exposure to ISL or LEN, serious infections within the last month, hepatitis B or C co-infections, low kidney function or certain low blood cell counts.

What is being tested?

The study tests the effectiveness of taking Islatravir (ISL) orally once a week combined with Lenacapavir (LEN) in those whose HIV is already under control. The goal is to see how well this combination works after 24 weeks compared to their current treatment.

What are the potential side effects?

While specific side effects are not listed here, common side effects from HIV treatments like ISL and LEN may include nausea, headache, fatigue, and potential liver issues. Side effects can vary based on individual health conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My HIV-1 levels have been undetectable or very low for at least 24 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously used or been exposed to islatravir or lenacapavir.

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My kidney function is low, with a creatinine clearance of 30 mL/min or less.

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My HIV treatment failed to control the virus before.

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My HIV treatment has shown resistance to certain medications.

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I have tested positive for hepatitis B.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 up to week 36

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 up to week 36

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 up to week 36 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

PK Parameter: AUCtau of ISL and LEN

PK Parameter: Ctau of ISL and LEN

PK Parameter: Tmax of ISL and LEN

+2 more

Side effects data

From 2023 Phase 3 trial • 35 Patients • NCT04233216

36%

Lymphocyte count decreased

29%

COVID-19

29%

Diarrhoea

21%

Creatinine renal clearance decreased

14%

Rash

14%

Arthralgia

14%

Accidental overdose

14%

Cough

14%

Upper respiratory tract infection

14%

Nausea

14%

Headache

14%

Fatigue

Urinary tract infection

Sleep terror

Postoperative wound infection

Anaemia

Obesity

Abdominal pain lower

Anal rash

Nocturnal hypertension

Oropharyngeal pain

Alanine aminotransferase increased

Mitral valve incompetence

Ear pain

Constipation

Cellulitis

Epididymitis

Hordeolum

Onychomycosis

Otitis externa

Decreased appetite

Joint effusion

Kaposi's sarcoma

Dysuria

Haematuria

Castleman's disease

Amoebiasis

Blood cholesterol increased

Night sweats

C-reactive protein increased

Myelopathy

Eye irritation

Motor dysfunction

Intestinal transit time increased

Humerus fracture

Memory impairment

Respiratory tract infection viral

Blood calcium increased

Blood glucose increased

Abdominal pain

Device dislocation

Blood creatine phosphokinase increased

Exposure to communicable disease

Chest pain

Pyrexia

Proteinuria

Pancytopenia

Dry eye

Skin candida

Anaemia postoperative

Hypertension

Intermittent claudication

Peripheral arterial occlusive disease

100%

80%

60%

40%

20%

Study treatment Arm

DOR+ART

Placebo+ART

DOR/ISL+ART

ISL+ART

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: ISL+LENExperimental Treatment2 Interventions

Participants will receive the following for at least 48 weeks: * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg (2 x 1 mg)

Group II: B/F/TAFExperimental Treatment3 Interventions

Participants will receive the following for at least 48 weeks: * bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

B/F/TAF

2016

Completed Phase 4

~5170

ISL

2021

Completed Phase 3

~530

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Nucleoside Reverse Transcriptase Translocation Inhibitors (NRTTIs) like Islatravir work by integrating into the viral DNA during replication, causing premature chain termination and halting viral multiplication. Capsid Inhibitors such as Lenacapavir disrupt the HIV capsid, which is vital for protecting the viral RNA and enzymes necessary for replication. These mechanisms are crucial for HIV patients as they effectively suppress the virus, reduce viral load, and prevent disease progression, thereby improving quality of life and reducing the risk of transmission.

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