CNS Reservoir in HIV Not Affected by Timing of ART initiation During Chronic Infection

Residual CNS immune activation was not correlated with pretreatment immune status in HIV-positive patients who initiated ART during chronic infection, indicating that the CNS reservoir is not differentially affected by the timing of ART initiation.

Results of a study published in Open Forum Infectious Diseases showed no correlation between residual immune central nervous system (CNS) immune activation and pretreatment immune status among patients with HIV infection who initiated antiretroviral therapy (ART) during chronic infection.

Researchers at the University of Gothenburg in Sweden sourced patient data for this study from the longitudinal Gothenburg HIV CSF Study Cohort. In this study, the researchers retrospectively identified a subset of neuroasymptomatic, treatment-naïve or off-treatment (>1 year) patients (N=183) with HIV Infection. Included patients were those who initiated suppressive ART during chronic infection and had cerebrospinal fluid (CSF) and serum samples collected at baseline and between years 1 and 3 after ART initiation. Patients were evaluated for CNS reservoir changes. The chronic phase of HIV infection was defined as more than 1 year after transmission, and viral suppression was defined as a viral load of less than 50 c/mL. In addition, transient increases in plasma viral load (HIV RNA, <500 copies/mL) viral were considered a “viral blip.”

Among patients included in the analysis, the median age at ART initiation was 39.8 (IQR, 32.9-48.4) years, 38% were women, the median pre-ART CD4+ T-cell count was 240 (IQR, 120-332.3) cells/µL, and the median plasma HIV RNA level was 4.9 (IQR, 4.3-5.6) log10 copies/mL. In addition, CSF analysis showed a median HIV RNA level of 3.77 (IQR, 3.16-4.39) log10 copies/mL, and a median leukocyte count of 4.00 (IQR, 1-8) WBCs/mm3.

A total of 12 patients experienced a viral blip during the study period, with a median viral load of 112 (range, 56-489) c/mL at 1 year and 58 (range, 52-63) c/mL at 3 years or more on ART. No patient had more than 1 viral blip event, and viral suppression was maintained at all other assessments.

At 1 year following ART initiation, CSF analysis showed an HIV RNA viral load of more than 20 copies/mL in 7% of patients, with no corresponding increase in plasma levels. Similar findings were observed at 3 years.

The clinical importance of residual CNS immune activation, and the potential benefit of reduction of reservoir size by very early ART remains unclear, and potential long term benefits need further investigation.

Significant correlations were observed between pretreatment CD4+ T-lymphocyte count and CSF neopterin levels (r, -0.28; P =.002), though these correlations were no longer significant at years 2 (r, -0.026; P =.8) or 3 (r, -0.063; P =.5). There also were significant correlations between CSF neopterin levels at baseline and those observed at year 1 (r, 0.37; P =.0001), but no correlations were observed at year 3. In multivariate analyses, CSF neopterin was potentially associated with assessment year, ART duration, age, and sex.

Trends in serum neopterin levels were similar to CSF levels.

The results of this study may not be generalizable to neurosymptomatic patients with HIV infection, as these individuals were excluded from the analysis.

According to the researchers, “The clinical importance of residual CNS immune activation, and the potential benefit of reduction of reservoir size by very early ART remains unclear, and potential long term benefits need further investigation.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Edén A, Rydberg F, Yilmaz A, et al. Residual CNS immune activation is not prevented by antiretroviral therapy initiated during early chronic HIV infection. Open Forum Infect Dis. Published online February 9, 2023. doi:10.1093/ofid/ofad064