New HIV Prevention: Cabotegravir Injection Shows Promise

observational-study PMID: 34379922

Quick Summary: A new injectable medication called cabotegravir (CAB-LA) was found to be more effective than daily pills at preventing HIV in men who have sex with men (MSM) and transgender women. This study showed a significant reduction in new HIV infections with the injection.

What The Research Found

This study compared a new HIV prevention method, an injection of cabotegravir (CAB-LA), to the daily pill often used for HIV prevention (TDF-FTC). The results showed that the cabotegravir injection was much better at preventing HIV. People who got the injection were less likely to get HIV compared to those taking the daily pill.

Study Details

Who was studied: The study included cisgender men who have sex with men (MSM) and transgender women who have sex with men who were at risk of getting HIV.

How long: Participants were followed for about three years (153 weeks).

What they took: One group received an injection of cabotegravir every two months. The other group took a daily pill.

What This Means For You

Better Protection: If you are an MSM or a transgender woman at risk for HIV, this injection could offer better protection than the daily pill.

Convenience: The injection only needs to be given every two months, which might be easier to manage than taking a pill every day.

Talk to Your Doctor: Discuss this new option with your doctor to see if it's right for you. They can help you understand the benefits and risks.

Study Limitations

Early Stop: The study was stopped early because the injection worked so well. This means we don't have as much information about the long-term effects.

Resistance: Some people who got HIV despite the injection showed signs of drug resistance. This means the virus changed and the medication might not work as well.

Side Effects: Many people who got the injection experienced reactions at the injection site.

Key Findings

The study concluded that long-acting injectable cabotegravir (CAB-LA) was superior to daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) in preventing HIV infection among at-risk cisgender men who have sex with men (MSM) and transgender women. CAB-LA reduced HIV incidence by 66% (hazard ratio: 0.34; 95% CI: 0.18–0.62) compared to TDF-FTC. However, cases of INSTI resistance and delayed HIV detection were observed in participants who contracted HIV despite CAB-LA exposure.

Study Design

This was a randomized, double-blind, double-dummy, noninferiority clinical trial (ClinicalTrials.gov: NCT02720094) with a median follow-up of 153 weeks. The intention-to-treat population included 4,566 participants (12.5% transgender women; median age 26 years, IQR: 22–32). The trial was halted early due to CAB-LA’s significant efficacy advantage.

Dosage & Administration

CAB-LA was administered intramuscularly at 600 mg every 8 weeks. The comparator was daily oral TDF-FTC. Both groups received placebo versions of the alternative regimen to maintain blinding.

Results & Efficacy

HIV incidence: 0.41 per 100 person-years (CAB-LA) vs. 1.22 per 100 person-years (TDF-FTC).
Hazard ratio: 0.34 (95% CI: 0.18–0.62; p < 0.001), indicating CAB-LA’s superior efficacy.
Consistency across subgroups: Efficacy was maintained in prespecified subgroups (e.g., age, race, geographic region).
Adverse events: Injection-site reactions occurred in 81.4% of CAB-LA recipients vs. 31.3% in TDF-FTC.

Limitations

Early termination: The trial was stopped after interim analysis, limiting long-term safety and efficacy data.
INSTI resistance: Emergence of resistance mutations in individuals who acquired HIV while exposed to CAB-LA raises concerns about treatment failure management.
Demographics: While 49.8% of U.S. participants were Black, global generalizability may be limited due to regional enrollment patterns (e.g., U.S. vs. international sites).
Observational design caveat: Though randomized, the study’s open-label extension phase (not detailed here) may introduce bias.

Clinical Relevance

CAB-LA offers a highly effective alternative to daily oral PrEP, particularly for populations with challenges adhering to daily pills. Its 8-week dosing interval could improve adherence and accessibility. However, clinicians must monitor for delayed HIV detection and INSTI resistance in cases of breakthrough infections. The high rate of injection-site reactions (81.4%) suggests the need for patient education on tolerability. These findings support CAB-LA as a promising option for HIV prevention in MSM and transgender women, but strategies to mitigate resistance and optimize long-term safety are critical.

Note: This analysis focuses solely on the HPTN 083 trial (NCT02720094) and does not extrapolate to other formulations or populations.