The LATTE-2 Week 256 results demonstrate long-acting injectable therapy maintains viral suppression for nearly five years
Imagine the mental load of taking a pill at the same time every day, for the rest of your life. Now, imagine trading that daily reminder for an appointment every two months. This isn't science fiction—it's the reality brought by a groundbreaking medical advancement in HIV treatment. For millions of people living with HIV, the psychological weight of daily medication can be as burdensome as the virus itself, with pill fatigue, stigma, and adherence challenges creating significant barriers to consistent treatment 2 .
Enter long-acting injectable therapy—a revolutionary approach that replaces daily pills with periodic injections. The LATTE-2 clinical trial, one of the most ambitious studies in HIV research, set out to answer a critical question: Could this convenient approach stand the test of time? The resounding answer, revealed in its Week 256 results, demonstrates not only that it works but that it continues to work effectively for nearly five years 1 .
This isn't just about convenience; it's about transforming what it means to live with HIV. By freeing individuals from the daily reminder of their status, long-acting injectables are reshaping HIV from a condition that requires constant management to one that can be addressed with periodic treatment. The LATTE-2 findings represent a paradigm shift in how we approach HIV care, offering a compelling alternative that aligns better with human behavior and preferences 3 .
The magic behind this breakthrough lies in the unique formulation of two powerful drugs: cabotegravir and rilpivirine. Cabotegravir belongs to a class of drugs called integrase strand transfer inhibitors, which block the virus from integrating its genetic material into human cells. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that prevents the virus from replicating. Together, they form a complete regimen that suppresses HIV through two different mechanisms 7 .
Scientists developed nanoparticle formulations of these drugs that are released slowly from the muscle tissue after injection.
The cabotegravir component forms a "depot" in the muscle, serving as a reservoir that steadily supplies the drug into the bloodstream 7 .
The LATTE-2 trial was designed with a practical, real-world approach. It followed an induction-maintenance model where participants first established viral suppression with a 20-week course of oral medication before being randomized to either continue oral therapy or switch to the injectable regimen administered either every four weeks or every eight weeks. This careful staging ensured participants could tolerate the medications before committing to the long-acting format 1 .
Conducted across 50 sites in North America and Europe, LATTE-2 was a phase 2b, randomized, open-label study that reflected real-world clinical practice. Its design allowed researchers to directly compare the long-term performance of the injectable regimen against traditional daily oral therapy 1 .
All participants started with daily oral cabotegravir plus two other antiretroviral drugs to rapidly achieve viral suppression.
Those successfully suppressed were divided into three groups—one continuing oral therapy, one switching to injections every 4 weeks, and one switching to injections every 8 weeks.
Participants continued their assigned treatments while researchers closely monitored viral suppression and side effects.
The long-term follow-up that provided the crucial five-year data that cemented the regimen's durability 1 .
| Phase | Duration | Oral Therapy Group | Every 4-Week Injection Group | Every 8-Week Injection Group |
|---|---|---|---|---|
| Induction | 20 weeks | Oral CAB + ABC/3TC | Oral CAB + ABC/3TC | Oral CAB + ABC/3TC |
| Maintenance | 96 weeks | Continued oral therapy | CAB 400mg + RPV 600mg LA injections | CAB 600mg + RPV 900mg LA injections |
| Extension | Through week 256 | Option to switch to injections | Continued injections | Continued injections |
This extended observation period was crucial for understanding how the treatment would perform over what essentially constitutes medium-term management of HIV—a time frame much more relevant to clinical reality than the shorter one-year outcomes typically reported in initial trials.
The Week 256 findings from LATTE-2 delivered compelling evidence for the long-term viability of injectable HIV therapy. After nearly five years of follow-up, 81% of participants in the groups that started injections early maintained viral suppression, with no cases of protocol-defined virologic failure occurring after week 48 1 . This demonstrates not just efficacy but remarkable consistency over time.
Perhaps even more impressive were the results from participants who switched from oral to injectable therapy later in the study. Among this group, a striking 93% maintained viral suppression after making the transition 1 . This high success rate suggests that the injectable regimen works well regardless of when people switch from oral medication, providing flexibility for both patients and clinicians.
| Participant Group | Number of Participants | With HIV-1 RNA <50 copies/mL | Percentage |
|---|---|---|---|
| Early Injection Groups (Q8W/Q4W) | 230 | 186 | 81% |
| Switch Groups (Oral to Injection) | 44 | 41 | 93% |
These impressive outcomes were achieved with a favorable safety profile. Over the entire five-year period, only a small percentage of participants (approximately 2%) discontinued treatment due to injection-related reactions 1 . The most common side effects were injection site reactions—including pain, swelling, or redness—which typically lessened in frequency and severity over time as patients continued with the injections 7 .
All medical treatments require balancing benefits against potential side effects, and long-acting HIV therapy is no exception. The LATTE-2 trial provided extensive safety data that helps clinicians and patients make informed decisions.
The most frequently reported side effects were injection site reactions (ISRs), which occurred in the majority of participants, especially during early injections. These typically included pain, swelling, and redness at the injection site but were generally mild to moderate in severity and temporary—usually resolving within a few days without intervention 7 . Importantly, these reactions became less frequent and bothersome over time as participants continued with the regimen.
| Safety Parameter | Early Injection Groups (n=230) | Switch Groups (n=44) |
|---|---|---|
| Discontinuation due to injection site reactions | 4 participants (2%) | 1 participant (2%) |
| Drug-related serious adverse events | 3 participants | 0 participants |
| Most common side effects | Injection site reactions (typically mild-moderate, transient) | Injection site reactions (typically mild-moderate, transient) |
Beyond injection site concerns, the systemic safety profile of the injectable regimen proved comparable to traditional oral antiretroviral therapy.
Injection site reactions became less frequent and bothersome over time as participants continued with the regimen.
Beyond injection site concerns, the systemic safety profile of the injectable regimen proved comparable to traditional oral antiretroviral therapy. Rates of serious adverse events were low, with only three participants in the early injection groups experiencing drug-related serious adverse events 1 . The types and frequencies of other side effects—such as headache, fever, or fatigue—were similar to those observed with oral medications, suggesting that the injectable format doesn't introduce new systemic safety concerns 7 .
One of the most significant advantages of long-acting injectable therapy is its potential to overcome the challenges of daily pill-taking. The LATTE-2 trial demonstrated exceptionally high adherence rates—a remarkable 96% of all injections were administered within the allowed 7-day window of the scheduled date through week 256 6 .
96% of injections administered within the 7-day window
Instances where oral bridge was used
All maintained viral suppression during interruptions
This impressive adherence translated directly to sustained virologic control. For the small number of planned treatment interruptions (such as for vacations or work conflicts), the study protocol provided oral cabotegravir and rilpivirine as a "bridge." In all 30 instances where this oral bridge was used, participants maintained viral suppression, demonstrating the flexibility of this approach for real-life situations 6 .
Real-world evidence emerging since the completion of LATTE-2 has reinforced these findings. A recent study from Germany following 102 people receiving long-acting cabotegravir and rilpivirine over 44 months confirmed that 97% maintained viral suppression, even though 82% experienced at least one injection delay 3 . This suggests that the high efficacy observed in clinical trials translates effectively to routine clinical practice.
The five-year data from LATTE-2 represents more than just another clinical trial result—it marks a fundamental shift in how we approach HIV treatment. By providing a validated, durable alternative to daily pill-taking, long-acting injectables address some of the most persistent challenges in HIV management.
For many people living with HIV, the most significant benefit may be psychological, reducing internalized stigma and improving quality of life.
High adherence rates contribute to preventing viral resistance and reducing community viral load at a population level 6 .
Research is already underway on even longer-acting formulations, including six-month regimens and novel combination therapies 5 .
| Component | Function in Study |
|---|---|
| Cabotegravir (oral and long-acting injectable) | Integrase strand transfer inhibitor that blocks HIV integration into human DNA |
| Rilpivirine (oral and long-acting injectable) | Non-nucleoside reverse transcriptase inhibitor that prevents viral replication |
| Abbott Real-Time HIV-1 Assay | Precise measurement of viral load (HIV-1 RNA) to confirm suppression |
| Intramuscular Injection Protocol | Standardized administration of long-acting formulations in gluteal muscle |
| Oral Lead-In Dosing | Assessment of tolerability before initiating injectable regimen |
The Week 256 results from the LATTE-2 trial represent a milestone in HIV care, demonstrating that long-acting injectable therapy with cabotegravir and rilpivirine isn't just a short-term alternative but a durable, effective maintenance treatment that stands the test of time. For nearly five years, participants maintained viral suppression with a convenient every-two-month dosing schedule that most found manageable and preferable to daily pills.
This breakthrough matters because it aligns HIV treatment with how people actually live their lives. By reducing pill burden, decreasing the visibility of treatment, and maintaining high adherence rates, long-acting injectables address both the medical and psychological aspects of living with HIV. As real-world experience continues to accumulate, this approach promises to expand treatment options and improve quality of life for millions of people worldwide.
The journey from daily multidrug regimens to simplified long-acting options exemplifies the remarkable progress in HIV science. With continued innovation and implementation, the future of HIV care looks increasingly flexible, patient-centered, and compatible with living a full, healthy life uninterrupted by daily medication.