COMPARATIVEEFFICACYANDSAFETYOF LONG-ACTING ANTIRETROVIRAL THERAPY IN HIV-1 MANAGEMENT: A NETWORK META-ANALYSIS
Author(s)
Omolayomi I. Kaska, PharmD1, Mahlet D. Tesfaye, PharmD1, Sarafina M. Phillips, MS1, Brian Rittenhouse, PhD1, Irene B. Murimi-Worstell, PhD1, Ismaeel U. Yunusa, PharmD, PhD2, Joanne Doucette, MS1, Tewodros Eguale, MD, PhD1;
1MCPHS University, Boston, MA, USA, 2University of South Carolina College of Pharmacy, Columbia, SC, USA
1MCPHS University, Boston, MA, USA, 2University of South Carolina College of Pharmacy, Columbia, SC, USA
OBJECTIVES: To assess whether long‑acting antiretroviral therapy (LA‑ART) regimens offer comparable virologic suppression and HIV‑1 prevention to standard oral therapies and compare their safety profiles across treatment‑naïve and treatment‑experienced populations.
METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library from inception to September 2025 identified randomized controlled trials comparing LA‑ART formulations with oral regimens for HIV‑1 treatment and prophylaxis. A random‑effects network meta‑analysis, adhering to PRISMA-NMA guidelines, was conducted to estimate relative risks, and surface under the cumulative ranking curves (SUCRA) quantified relative performance. Subgroup analyses compared treatment‑naïve versus experienced participants and 48‑ versus 96‑week treatment durations.
RESULTS: Among 4,893 participants in eight trials assessing virologic suppression, cabotegravir-based fixed dose regimen had the highest efficacy for virologic suppression (Relative Risk (RR) = 1.12, 95% C.I: 1.02 - 1.24). Long-acting cabotegravir-based injectable, dosed 8-weekly (RR = 1.05, 95% C.I: 1.01 - 1.08) and 4-weekly (RR = 1.03, 95% C.I: 1.00 - 1.06) showed higher, significant results than standard oral regimens. SUCRA rankings similarly favored long-acting regimens. Injection‑site reactions were more frequent with LA‑ART, but serious adverse events were comparable across regimens. Results from nine trials involving a total of 27,245 participants proved long‑acting lenacapavir and cabotegravir markedly reduced HIV‑1 incidence versus placebo or oral prophylaxis (RR = 0.04, 95% C.I: 0.00 - 0.84 and RR = 0.2, 95% C.I: 0.01 - 3.04, respectively). Stratified analyses showed consistent results across treatment‑naïve and experienced groups and between 48‑ and 96‑week durations.
CONCLUSIONS: These results showed that LA‑ART regimens provide higher efficacy than conventional oral combinations across treatment and prevention settings and may improve adherence through reduced dosing frequency. Despite increased incidence of injection‑site reactions, overall safety profiles were similar. These findings support incorporating LA‑ART into HIV‑1 management guidelines as a patient‑centered alternative for individuals struggling with adherence to pills.
METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library from inception to September 2025 identified randomized controlled trials comparing LA‑ART formulations with oral regimens for HIV‑1 treatment and prophylaxis. A random‑effects network meta‑analysis, adhering to PRISMA-NMA guidelines, was conducted to estimate relative risks, and surface under the cumulative ranking curves (SUCRA) quantified relative performance. Subgroup analyses compared treatment‑naïve versus experienced participants and 48‑ versus 96‑week treatment durations.
RESULTS: Among 4,893 participants in eight trials assessing virologic suppression, cabotegravir-based fixed dose regimen had the highest efficacy for virologic suppression (Relative Risk (RR) = 1.12, 95% C.I: 1.02 - 1.24). Long-acting cabotegravir-based injectable, dosed 8-weekly (RR = 1.05, 95% C.I: 1.01 - 1.08) and 4-weekly (RR = 1.03, 95% C.I: 1.00 - 1.06) showed higher, significant results than standard oral regimens. SUCRA rankings similarly favored long-acting regimens. Injection‑site reactions were more frequent with LA‑ART, but serious adverse events were comparable across regimens. Results from nine trials involving a total of 27,245 participants proved long‑acting lenacapavir and cabotegravir markedly reduced HIV‑1 incidence versus placebo or oral prophylaxis (RR = 0.04, 95% C.I: 0.00 - 0.84 and RR = 0.2, 95% C.I: 0.01 - 3.04, respectively). Stratified analyses showed consistent results across treatment‑naïve and experienced groups and between 48‑ and 96‑week durations.
CONCLUSIONS: These results showed that LA‑ART regimens provide higher efficacy than conventional oral combinations across treatment and prevention settings and may improve adherence through reduced dosing frequency. Despite increased incidence of injection‑site reactions, overall safety profiles were similar. These findings support incorporating LA‑ART into HIV‑1 management guidelines as a patient‑centered alternative for individuals struggling with adherence to pills.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO137
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Infectious Disease (non-vaccine), SDC: Reproductive & Sexual Health, STA: Multiple/Other Specialized Treatments