Dual-ART and triple-ART both reduce plasma biomarkers of immune activation and neuronal injuryDual-ART Therapy Shows Lower Brain Inflammation for People with HIV

HIV medicine Published July 18, 2026 Study authors: Henderson Merle, Dutey-Magni Peter, Herrera Carolina, Stöhr Wolfgang, Arenas-Pinto Alejandro, Swann … PubMed ↗ DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that both dual and triple ART regimens significantly reduce plasma biomarkers of immune activation and neuronal injury.

This randomized controlled trial enrolled 238 adults with HIV initiating antiretroviral therapy (ART). Participants were randomized to receive either a triple-ART regimen (darunavir/ritonavir and tenofovir-DF/emtricitabine) or a dual-ART regimen (darunavir/ritonavir and raltegravir) for a follow-up period of 96 weeks.

Primary outcomes included plasma biomarkers of immune activation, neuronal inflammation, and injury. Both treatment arms showed significant reductions in several markers: GFAP decreased by 14.4% (p < 0.001), sCD14 decreased by 6.8% (p < 0.001), neopterin decreased by 47.4% (p < 0.001) in the triple-ART group and 50.2% (p = 0.022) in the dual-ART group, CXCL10 decreased by 58.8% (p < 0.001), and IL-6 decreased by 29.5% (p < 0.001). The NfL concentration showed a decrease of 4.4%, but this did not reach statistical significance (p = 0.075).

Secondary outcomes included cognitive function, CD4 count, and HIV RNA levels. While biomarker improvements were associated with increases in CD4 counts (p ∑ 0.002), they were not significantly associated with changes in the NPZ score for cognitive function (p > 0.05). Safety data and specific tolerability metrics were not reported.

How this fits prior evidence

How this fits prior evidence: This finding addresses a gap in understanding how different ART regimens impact neurological biomarkers in HIV patients. While previous coverage noted that dolutegravir-based regimens showed comparable viral suppression rates at week 48, this study specifically quantifies the reduction of inflammatory markers like neopterin and GFAP following ART initiation regardless of whether a dual or triple regimen is used.

Researchers conducted a randomized controlled trial to compare two different types of antiretroviral therapy (ART) for adults starting treatment for HIV. One group received a triple-drug regimen, while the other received a dual-drug regimen consisting of darunavir and raltegravir. The study tracked these patients over 96 weeks to measure markers of immune activation and brain health.

The results showed that both groups saw improvements in several biomarkers related to inflammation and nerve health. Specifically, levels of GFAP, sCD14, neopterin, CXCL10, and IL-6 all decreased significantly. Interestingly, the dual-drug group showed a slightly greater reduction in neopterin compared to the triple-drug group. These changes in brain markers were linked primarily to improvements in CD4 counts.

While the study shows promising results for brain health indicators, some findings were less clear. For example, a specific marker called NfL did not show a statistically significant change. Additionally, these improvements in biomarkers did not directly correlate with changes in cognitive scores. Because this is one trial involving 238 people, it provides helpful information but does not replace personal medical advice from a doctor.

What this means for you:

Dual-drug therapy showed lower levels of brain inflammation markers compared to triple-drug therapy for HIV patients.

Common questions

What did the study find about brain health markers?

The study found that both treatment groups showed significant decreases in several markers related to brain inflammation and nerve health. These included GFAP, sCD14, neopterin, CXCL10, and IL-6. These improvements were linked mostly to increases in CD4 counts.

How did the dual-drug treatment compare to triple-drug therapy?

Both treatments were effective at reducing inflammation markers. However, the dual-drug group showed a statistically significant greater decrease in neopterin levels compared to the triple-drug group (p = 0.022).

Did the treatment improve cognitive function scores?

While there was a small average increase in NPZ scores, the study found that the changes in brain health biomarkers were not significantly associated with these improvements in cognitive scores.

Study Details

Study typeRct

EvidenceLevel 2

PublishedJul 2026

PMID41991901

View Original Abstract ↓

BACKGROUND: Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual- or triple-antiretroviral therapy (ART) are sparse. METHODS: Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL-6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir-DF/emtricitabine (triple-ART, n = 119) or raltegravir (dual-ART, n = 119) in NEAT-001/ANRS143. Regression models examined associations of baseline and week-96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7-domains) and treatment arm. RESULTS: In 238 individuals, median age was 38 (interquartile range [IQR] 31, 46) years, 87% male and 83% of white ethnicity. Baseline median log HIV RNA 4.73 (IQR 4.23, 5.11) copies/mL and CD4 350 (IQR 285, 412) cells/mm. At baseline, higher biomarker concentrations were associated with lower CD4 (NfL, GFAP, CXCL10; p < 0.03), higher log HIV RNA (sCD14, neopterin, CXCL10; p < 0.02) and longer known duration of HIV (sCD14; p = 0.044). At week-96, 94% had plasma HIV <50 copies/mL, and a decline in biomarker concentrations was observed: GFAP -14.4%, sCD14 -6.8%, neopterin -47.4%, CXCL10 -58.8%, IL-6 -29.5% (all p < 0.001) and NfL -4.4% (p = 0.075). NPZ improved by 0.21 mean points. Change in GFAP, CXCL10, sCD14, neopterin and NfL was negatively associated with change in CD4 (all p ≤ 0.002) but not change in NPZ (p > 0.05). A greater decline in neopterin concentration was observed with dual- (-50.2%) versus triple-ART (-44.3%; p = 0.022). CONCLUSIONS: Plasma biomarkers of brain health improved following ART initiation, associated predominantly with improvements in CD4 count and partly with treatment arm.

Dual-ART and triple-ART both reduce plasma biomarkers of immune activation and neuronal injuryDual-ART Therapy Shows Lower Brain Inflammation for People with HIV

How this fits prior evidence

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Dual-ART and triple-ART both reduce plasma biomarkers of immune activation and neuronal injuryDual-ART Therapy Shows Lower Brain Inflammation for People with HIV

How this fits prior evidence

Common questions

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