Neurocognitive Impairment in ART-Experienced People Living with HIV: An Analysis of Clinical Risk Factors, Injection Drug Use, and the sCD163

Background: In people living with HIV (PLHIV), ongoing neuronal injury has shown a correlation with elevated levels of soluble markers of immune activation, such as sCD163. Additionally, various risk factors, such as injection drug use (IDU), can independently affect immune and cognitive functions, leading to neurocognitive impairment (NCI). However, the potential sCD163-IDU-NCI axis in ART-experienced PLHIV is not clear. This study aims to determine NCI prevalence and investigate the interplay between risk factors and sCD163 in Pakistani PLHIV. Methods: For this cross-sectional study, 150 PLHIV and 30 HIV-negative people who inject drugs (PWID) were recruited using a convenience sampling strategy. NCI screening was performed using the International HIV Dementia Scale (IHDS) tool. Blood samples from PLHIV were used to perform HIV recency testing using the Asante Rapid Recency Assay, and to evaluate sCD163 levels using ELISA. Sociodemographic and clinical data were collected from medical records. Subsequently, descriptive statistics were used to summarize data variables, while comparisons (two and multiple groups) between participants with and without NCI were conducted, respectively, using the Mann–Whitney test or Kruskal–Wallis test for continuous variables, and Fisher’s exact test for categorial variables. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the discriminative ability of sCD163. Logistic regression was used to identify predictors of neurocognitive impairment. Results: The majority of PLHIV had IDU as a high-risk behavior. In PLHIV, the median age was 34.5 years (IQR: 30–41), ART duration was 35 months (IQR: 17–54), and median CD4 count was 326.5 cells/µL (IQR: 116–545.5). Long-term infections (>6 months post-seroconversion; median ART duration: 35 months; median CD4 counts: 326.5 cells/μL) were noted in 83.3% of PLHIV. IHDS-based screening showed that 83.33% (all PLHIV) and 50% (PLHIV with no IDU history) scored ≤ 9 on the IHDS, suggestive of NCI. IHDS-component analysis showed the memory recall to be significantly affected in PLHIV compared to controls (median score 3.2 versus 3.7, respectively, p < 0.001). Regression analysis showed only long-term infection (OR: 2.99, p = 0.03) to be significantly associated with neurocognitive impairment. sCD163 levels were significantly lower in PLHIV with NCI (mean = 7.48 ng/mL, SD = 7.05) compared to those without NCI (mean = 14.82 ng/mL, SD = 8.23; p < 0.0001), with an AUC of 0.803 (95% CI: 0.72–0.88). However, after adjusting for IDU history, the regression analysis showed an odds ratio for sCD163 of 0.998 (95% CI: 0.934, 1.067, p = 0.957), indicating no association between sCD163 levels and NCI. Conclusion: This study reports a high prevalence of NCI in Pakistani PLHIV, and no association between sCD163 and neurocognitive impairment in PLHIV after adjustment for a history of IDU. Long-term infection and IDU were significantly linked to NCI, while only IDU was associated with lower sCD163 levels, regardless of NCI.